ORCID Profile
0000-0002-7231-9446
Current Organisations
University of Technology Sydney
,
TU-Eindhoven
,
Eindhoven University of Technology
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biochemistry and Cell Biology | Biochemistry and Cell Biology not elsewhere classified | Bioinformatics Software | Proteomics and Intermolecular Interactions (excl. Medical Proteomics) | Artificial Intelligence and Image Processing | Pattern Recognition and Data Mining | Bioinformatics | Cell Development, Proliferation and Death | Systems Biology |
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Biological Sciences | Application Software Packages (excl. Computer Games) | Cancer and Related Disorders | Health not elsewhere classified | Infectious Diseases
Related Links
Publications
Rule discovery and distance separation to detect reliable miRNA biomarkers for the diagnosis of lung squamous cell carcinoma.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
HSP90 Protein Stabilizes Unloaded Argonaute Complexes and Microscopic P-bodies in Human Cells
Publisher: American Society for Cell Biology (ASCB)
Date: 05-2010
Abstract: Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.
tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression.
Publisher: MDPI AG
Date: 27-11-2015
DOI: 10.3390/LIFE5041638
Instance-based error correction for short reads of disease-associated genes
Publisher: Springer Science and Business Media LLC
Date: 02-06-2021
DOI: 10.1186/S12859-021-04058-Y
Abstract: Genomic reads from sequencing platforms contain random errors. Global correction algorithms have been developed, aiming to rectify all possible errors in the reads using generic genome-wide patterns. However, the non-uniform sequencing depths hinder the global approach to conduct effective error removal. As some genes may get under-corrected or over-corrected by the global approach, we conduct instance-based error correction for short reads of disease-associated genes or pathways. The paramount requirement is to ensure the relevant reads, instead of the whole genome, are error-free to provide significant benefits for single-nucleotide polymorphism (SNP) or variant calling studies on the specific genes. To rectify possible errors in the short reads of disease-associated genes, our novel idea is to exploit local sequence features and statistics directly related to these genes. Extensive experiments are conducted in comparison with state-of-the-art methods on both simulated and real datasets of lung cancer associated genes (including single-end and paired-end reads). The results demonstrated the superiority of our method with the best performance on precision, recall and gain rate, as well as on sequence assembly results (e.g., N50, the length of contig and contig quality). Instance-based strategy makes it possible to explore fine-grained patterns focusing on specific genes, providing high precision error correction and convincing gene sequence assembly. SNP case studies show that errors occurring at some traditional SNP areas can be accurately corrected, providing high precision and sensitivity for investigations on disease-causing point mutations.
Polypyrimidine Tract Binding Protein (hnRNP I) Is Possibly a Conserved Modulator of miRNA-Mediated Gene Regulation
Publisher: Public Library of Science (PLoS)
Date: 09-03-2012
Biography of Dr Gyorgy Hutvagner
Publisher: Springer Science and Business Media LLC
Date: 09-10-2006
miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity
Publisher: Public Library of Science (PLoS)
Date: 26-04-2013
Molecular markers associated with leptinine production are located on chromosome 1 in Solanum chacoense
Publisher: Springer Science and Business Media LLC
Date: 05-2001
Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells
Publisher: Rockefeller University Press
Date: 30-06-2008
Abstract: Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA in primary cell growth, we generated Dicer-conditional mice. Ablation of Dicer and loss of mature miRNAs in embryonic fibroblasts up-regulated p19Arf and p53 levels, inhibited cell proliferation, and induced a premature senescence phenotype that was also observed in vivo after Dicer ablation in the developing limb and in adult skin. Furthermore, deletion of the Ink4a/Arf or p53 locus could rescue fibroblasts from premature senescence induced by Dicer ablation. Although levels of Ras and Myc oncoproteins appeared unaltered, loss of Dicer resulted in increased DNA damage and p53 activity in these cells. These results reveal that loss of miRNA biogenesis activates a DNA damage checkpoint, up-regulates p19Arf-p53 signaling, and induces senescence in primary cells.
Another Loophole in miRNA processing
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.MOLCEL.2011.10.010
Abstract: In this issue of Molecular Cell, Suzuki et al. (2011) present the intriguing finding that an RNAse known to play an important role in immunity regulates miRNA processing in cancer and inflammation by cleaving the terminal loops of many miRNAs.
An isomiR expression panel based novel breast cancer classification approach using improved mutual information
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Computational analysis, biochemical purification, and detection of tRNA-derived small RNA fragments.
Publisher: Springer New York
Date: 2014
DOI: 10.1007/978-1-4939-0931-5_14
Abstract: The rapidly growing list of small RNA species generated by next-generation sequencing technologies has accelerated the development of new bioinformatics tools for their detection. Small RNAs generated from tRNAs, transfer RNA-derived fragments (tRFs), represent a novel challenge in accurately identifying and distinguishing them from random degradation products of tRNAs. Here, we describe a bioinformatics approach to detect tRFs in next-generation sequencing libraries. We also present a biochemical purification protocol for enriching 5' tRFs and separating them from miRNAs. And finally, we suggest reliable methods for detecting and quantifying tRFs.
Isolation and characterization of a water-stress-inducible cDNA clone from Solanum chacoense
Publisher: Springer Science and Business Media LLC
Date: 02-1995
DOI: 10.1007/BF00019324
tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation
Publisher: American Chemical Society (ACS)
Date: 12-12-2017
DOI: 10.1021/ACS.JPROTEOME.6B00267
Abstract: The functionality of small RNAs from abundant species of "housekeeping" noncoding RNAs (e.g., rRNA, tRNA, snRNA, snoRNA, etc.) remains a highly studied topic. The current state of research on short RNAs derived from transfer RNA (tRNA), called tRNA-derived fragments (tRFs), has been restricted largely to expression studies and limited functional studies. 5' tRFs are known translational inhibitors in mammalian cells, yet little is known about their functionality. Here we report on the first experimental evidence of the tRF protein interactome, identifying the mammalian multisynthetase complex as the primary interactor of the 5' tRF Gln19. We also present proteome-wide SILAC evidence that 5' tRFs increase ribosomal and poly(A)-binding protein translation.
MicroRNAs and cancer: Issue summary
Publisher: Springer Science and Business Media LLC
Date: 09-10-2006
Non-Coding RNAs in Pediatric Solid Tumors.
Publisher: Frontiers Media SA
Date: 20-09-2019
Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins
Publisher: Portland Press Ltd.
Date: 13-05-2010
DOI: 10.1042/BJ20100024
Abstract: Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in protein expression as a result of altered transcription or translation. To determine whether neurotrophins regulate the production of microRNAs (miRNAs), small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify BDNF (brain-derived neurotrophic factor)-induced miRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the miRNAs most responsive to BDNF treatment. This cluster was found to produce four miRNAs: miR-132, miR-132*, miR-212 and miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 miRNA cluster and the miRNAs derived from it are regulated by the ERK1/2 (extracellular-signalregulated kinase 1/2) pathway, via both MSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms.
Regulation of miRNA transcription in macrophages in response to candida albicans
Publisher: Public Library of Science (PLoS)
Date: 27-10-2010
A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation
Publisher: Springer Science and Business Media LLC
Date: 11-02-2019
DOI: 10.1038/S41467-019-08487-5
Abstract: Most metazoan embryos commence development with rapid, transcriptionally silent cell isions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri- miR430 and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.
The COVID-19 pandemic and healthcare systems in Africa: a scoping review of preparedness, impact and response
Publisher: BMJ
Date: 12-2021
DOI: 10.1136/BMJGH-2021-007179
Abstract: The COVID-19 pandemic has overwhelmed health systems in both developed and developing nations alike. Africa has one of the weakest health systems globally, but there is limited evidence on how the region is prepared for, impacted by and responded to the pandemic. We conducted a scoping review of PubMed, Scopus, CINAHL to search peer-reviewed articles and Google, Google Scholar and preprint sites for grey literature. The scoping review captured studies on either preparedness or impacts or responses associated with COVID-19 or covering one or more of the three topics and guided by Arksey and O’Malley’s methodological framework. The extracted information was documented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension checklist for scoping reviews. Finally, the resulting data were thematically analysed. Twenty-two eligible studies, of which 6 reported on health system preparedness, 19 described the impacts of COVID-19 on access to general and essential health services and 7 focused on responses taken by the healthcare systems were included. The main setbacks in health system preparation included lack of available health services needed for the pandemic, inadequate resources and equipment, and limited testing ability and surge capacity for COVID-19. Reduced flow of patients and missing scheduled appointments were among the most common impacts of the COVID-19 pandemic. Health system responses identified in this review included the availability of telephone consultations, re-purposing of available services and establishment of isolation centres, and provisions of COVID-19 guidelines in some settings. The health systems in Africa were inadequately prepared for the pandemic, and its impact was substantial. Responses were slow and did not match the magnitude of the problem. Interventions that will improve and strengthen health system resilience and financing through local, national and global engagement should be prioritised.
MicroRNA (miRNA)-to-miRNA Regulation of Programmed Cell Death 4 (PDCD4).
Publisher: Informa UK Limited
Date: 09-2019
DOI: 10.1128/MCB.00086-19
Author Correction: Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer
Publisher: Springer Science and Business Media LLC
Date: 21-05-2021
Long non-coding RNAs harboring miRNA seed regions are enriched in prostate cancer exosomes
Publisher: Springer Science and Business Media LLC
Date: 22-04-2016
DOI: 10.1038/SREP24922
Abstract: Long non-coding RNAs (lncRNAs) form the largest transcript class in the human transcriptome. These lncRNA are expressed not only in the cells, but they are also present in the cell-derived extracellular vesicles such as exosomes. The function of these lncRNAs in cancer biology is not entirely clear, but they appear to be modulators of gene expression. In this study, we characterize the expression of lncRNAs in several prostate cancer exosomes and their parental cell lines. We show that certain lncRNAs are enriched in cancer exosomes with the overall expression signatures varying across cell lines. These exosomal lncRNAs are themselves enriched for miRNA seeds with a preference for let-7 family members as well as miR-17, miR-18a, miR-20a, miR-93 and miR-106b. The enrichment of miRNA seed regions in exosomal lncRNAs is matched with a concomitant high expression of the same miRNA. In addition, the exosomal lncRNAs also showed an over representation of RNA binding protein binding motifs. The two most common motifs belonged to ELAVL1 and RBMX. Given the enrichment of miRNA and RBP sites on exosomal lncRNAs, their interplay may suggest a possible function in prostate cancer carcinogenesis.
Frontiers in Nanomedicine
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 15-04-2015
Small RNAs derived from the 5' end of tRNAs can inhibit protein translation in human cells
Publisher: Informa UK Limited
Date: 04-2013
DOI: 10.4161/RNA.24285
MiRTar2GO
Publisher: Oxford University Press (OUP)
Date: 28-11-2017
DOI: 10.1093/NAR/GKW1185
Single-cell multi-omics sequencing: application trends, COVID-19, data analysis issues and prospects
Publisher: Oxford University Press (OUP)
Date: 10-06-2021
DOI: 10.1093/BIB/BBAB229
Abstract: Single-cell sequencing is a biotechnology to sequence one layer of genomic information for in idual cells in a tissue s le. For ex le, single-cell DNA sequencing is to sequence the DNA from every single cell. Increasing in complexity, single-cell multi-omics sequencing, or single-cell multimodal omics sequencing, is to profile in parallel multiple layers of omics information from a single cell. In practice, single-cell multi-omics sequencing actually detects multiple traits such as DNA, RNA, methylation information and/or protein profiles from the same cell for many in iduals in a tissue s le. Multi-omics sequencing has been widely applied to systematically unravel interplay mechanisms of key components and pathways in cell. This survey overviews recent developments in single-cell multi-omics sequencing, and their applications to understand complex diseases in particular the COVID-19 pandemic. We also summarize machine learning and bioinformatics techniques used in the analysis of the intercorrelated multilayer heterogeneous data. We observed that variational inference and graph-based learning are popular approaches, and Seurat V3 is a commonly used tool to transfer the missing variables and labels. We also discussed two intensively studied issues relating to data consistency and ersity and commented on currently cared issues surrounding the error correction of data pairs and data imputation methods. The survey is concluded with some open questions and opportunities for this extraordinary field.
The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans
Publisher: EMBO
Date: 28-04-2011
Key MicroRNA’s and Their Targetome in Adrenocortical Cancer
Publisher: MDPI AG
Date: 06-08-2020
Abstract: Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics.
Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer
Publisher: Springer Science and Business Media LLC
Date: 12-04-2021
DOI: 10.1038/S41597-021-00884-0
Abstract: Progesterone receptor (PR) isoforms, PRA and PRB, act in a progesterone-independent and dependent manner to differentially modulate the biology of breast cancer cells. Here we show that the differences in PRA and PRB structure facilitate the binding of common and distinct protein interacting partners affecting the downstream signaling events of each PR-isoform. Tet-inducible HA-tagged PRA or HA-tagged PRB constructs were expressed in T47DC42 (PR/ER negative) breast cancer cells. Affinity purification coupled with stable isotope labeling of amino acids in cell culture (SILAC) mass spectrometry technique was performed to comprehensively study PRA and PRB interacting partners in both unliganded and liganded conditions. To validate our findings, we applied both forward and reverse SILAC conditions to effectively minimize experimental errors. These datasets will be useful in investigating PRA- and PRB-specific molecular mechanisms and as a database for subsequent experiments to identify novel PRA and PRB interacting proteins that differentially mediated different biological functions in breast cancer.
Cross disease analysis of co-functional microRNA pairs on a reconstructed network of disease-gene-microRNA tripartite.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2017
Regulation of miRNA processing and miRNA mediated gene repression in diseases.
Publisher: Bentham Science Publishers Ltd.
Date: 31-07-2014
Density-based detection of cell transition states to construct disparate and bifurcating trajectories
Publisher: Oxford University Press (OUP)
Date: 16-09-2022
DOI: 10.1093/NAR/GKAC785
Abstract: Tree- and linear-shaped cell differentiation trajectories have been widely observed in developmental biologies and can be also inferred through computational methods from single-cell RNA-sequencing datasets. However, trajectories with complicated topologies such as loops, disparate lineages and bifurcating hierarchy remain difficult to infer accurately. Here, we introduce a density-based trajectory inference method capable of constructing erse shapes of topological patterns including the most intriguing bifurcations. The novelty of our method is a step to exploit overlapping probability distributions to identify transition states of cells for determining connectability between cell clusters, and another step to infer a stable trajectory through a base-topology guided iterative fitting. Our method precisely re-constructed various benchmark reference trajectories. As a case study to demonstrate practical usefulness, our method was tested on single-cell RNA sequencing profiles of blood cells of SARS-CoV-2-infected patients. We not only re-discovered the linear trajectory bridging the transition from IgM plasmablast cells to developing neutrophils, and also found a previously-undiscovered lineage which can be rigorously supported by differentially expressed gene analysis.
Isolation and sequence analysis of a cDNA and a related gene for cytochrome P450 proteins from Solanum chacoense
Publisher: Elsevier BV
Date: 04-1997
DOI: 10.1016/S0378-1119(96)00819-0
Abstract: Inosine-containing degenerate PCR primers corresponding to the heme-binding domain of cytochrome P450 proteins have been synthesized and used for cloning cDNAs by the RT-PCR technique from Solanum chacoense. One clone in which the primer was immediately followed by sequences corresponding to the remaining part of the conserved domain was obtained. A leaf cDNA and a genomic library were constructed from S. chacoense. Clones homologous to the PCR fragment were isolated by plaque hybridization from both libraries (CYPs.ch-1 and CYPs.ch-2, respectively). Based on DNA sequence analysis, the selected clones are 87.6% identical and belong to the CYP71 family. The CYPs.ch genes are present in multiple copies in the S. chacoense as well as in the S. tuberosum genome with some polymorphisms. The CYPs.ch transcripts are slightly induced by methyl jasmonate and abscisic acid in S. chacoense foliage.
An evolutionarily conserved, alternatively spliced, intron in the p68/DDX5 DEAD-box RNA helicase gene encodes a novel miRNA
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2011
DOI: 10.1261/RNA.2591611
Abstract: The DEAD-box RNA helicase p68 (DDX5) plays important roles in several cellular processes, including transcription, pre-mRNA processing, and microRNA (miRNA) processing. p68 expression is growth and developmentally regulated, and alterations in p68 expression and/or function have been implicated in tumor development. The p68 gene encodes an evolutionarily conserved, alternatively spliced, intron the function of which has to date remained unclear. Although the intron-containing p68 RNA does not appear to yield an alternative p68 protein, it is differentially expressed in cell lines and tissues, indicating regulation of expression. Here we show that the p68 conserved intron encodes a novel putative miRNA, suggesting a previously unknown possible regulatory function for the p68 intron. We show that this miRNA (referred to as p68 miRNA) is processed from the intron via the canonical miRNA-processing pathway and that it associates with the Argonaute protein Ago2. Finally we show that the p68 miRNA suppresses an mRNA bearing complementary target sequences, suggesting that it is functional. These findings suggest a novel mechanism by which alterations in p68 expression may impact on the cell.
Argonaute proteins: key players in RNA silencing
Publisher: Springer Science and Business Media LLC
Date: 2008
DOI: 10.1038/NRM2321
Abstract: During the past decade, small non-coding RNAs have rapidly emerged as important contributors to gene regulation. To carry out their biological functions, these small RNAs require a unique class of proteins called Argonautes. The discovery and our comprehension of this highly conserved protein family is closely linked to the study of RNA-based gene silencing mechanisms. With their functional domains, Argonaute proteins can bind small non-coding RNAs and control protein synthesis, affect messenger RNA stability and even participate in the production of a new class of small RNAs, Piwi-interacting RNAs.
Asymmetry in the Assembly of the RNAi Enzyme Complex
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/S0092-8674(03)00759-1
Abstract: A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.
Biogenesis and the regulation of the maturation of miRNAs
Publisher: Portland Press Ltd.
Date: 30-04-2013
DOI: 10.1042/BSE0540017
Abstract: Regulation of gene expression is a fundamental process in both prokaryotic and eukaryotic organisms. Multiple regulatory mechanisms are in place to control gene expression at the level of transcription, post-transcription and post-translation to maintain optimal RNA and protein expressions in cells. miRNAs (microRNAs) are abundant short 21–23 nt non-coding RNAs that are key regulators of virtually all eukaryotic biological processes. The levels of miRNAs in an organism are crucial for proper development and sustaining optimal cell functions. Therefore the processing and regulation of the processing of these miRNAs are critical. In the present chapter we highlight the most important steps of miRNA processing, describe the functions of key proteins involved in the maturation of miRNAs, and discuss how the generation and the stability of miRNAs are regulated.
Acetyl-α-d-mannopyranose based cationic polymer via RAFT polymerization for lectin and nucleic acid bindings
Publisher: Wiley
Date: 22-02-2017
DOI: 10.1002/APP.44947
Posttranslational modification of Argonautes and their role in small RNA mediated gene regulation
Publisher: Springer Science and Business Media LLC
Date: 2011
Aberration-corrected ultrafine analysis of miRNA reads at single-base resolution: a k-mer lattice approach
Publisher: Oxford University Press (OUP)
Date: 21-07-2021
DOI: 10.1093/NAR/GKAB610
Abstract: Raw sequencing reads of miRNAs contain machine-made substitution errors, or even insertions and deletions (indels). Although the error rate can be low at 0.1%, precise rectification of these errors is critically important because isoform variation analysis at single-base resolution such as novel isomiR discovery, editing events understanding, differential expression analysis, or tissue-specific isoform identification is very sensitive to base positions and copy counts of the reads. Existing error correction methods do not work for miRNA sequencing data attributed to miRNAs’ length and per-read-coverage properties distinct from DNA or mRNA sequencing reads. We present a novel lattice structure combining kmers, (k – 1)mers and (k + 1)mers to address this problem. The method is particularly effective for the correction of indel errors. Extensive tests on datasets having known ground truth of errors demonstrate that the method is able to remove almost all of the errors, without introducing any new error, to improve the data quality from every-50-reads containing one error to every-1300-reads containing one error. Studies on experimental miRNA sequencing datasets show that the errors are often rectified at the 5′ ends and the seed regions of the reads, and that there are remarkable changes after the correction in miRNA isoform abundance, volume of singleton reads, overall entropy, isomiR families, tissue-specific miRNAs, and rare-miRNA quantities.
RNA Binding Proteins in the miRNA Pathway.
Publisher: MDPI AG
Date: 26-12-2015
DOI: 10.3390/IJMS17010031
RNAi: nature abhors a double-strand
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0959-437X(02)00290-3
Abstract: In organisms as erse as nematodes, trypanosomes, plants, and fungi, double-stranded RNA triggers the destruction of homologous mRNAs, a phenomenon known as RNA interference. RNA interference begins with the transformation of the double-stranded RNA into small RNAs that then guide a protein nuclease to destroy their mRNA targets.
Sequence-Specific Inhibition of Small RNA Function
Publisher: Public Library of Science (PLoS)
Date: 24-02-2004
Construction of competing endogenous RNA networks from paired RNA-seq data sets by pointwise mutual information.
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S12864-019-6321-X
Abstract: A long noncoding RNA (lncRNA) can act as a competing endogenous RNA (ceRNA) to compete with an mRNA for binding to the same miRNA. Such an interplay between the lncRNA, miRNA, and mRNA is called a ceRNA crosstalk. As an miRNA may have multiple lncRNA targets and multiple mRNA targets, connecting all the ceRNA crosstalks mediated by the same miRNA forms a ceRNA network. Methods have been developed to construct ceRNA networks in the literature. However, these methods have limits because they have not explored the expression characteristics of total RNAs. We proposed a novel method for constructing ceRNA networks and applied it to a paired RNA-seq data set. The first step of the method takes a competition regulation mechanism to derive candidate ceRNA crosstalks. Second, the method combines a competition rule and pointwise mutual information to compute a competition score for each candidate ceRNA crosstalk. Then, ceRNA crosstalks which have significant competition scores are selected to construct the ceRNA network. The key idea, pointwise mutual information, is ideally suitable for measuring the complex point-to-point relationships embedded in the ceRNA networks. Computational experiments and results demonstrate that the ceRNA networks can capture important regulatory mechanism of breast cancer, and have also revealed new insights into the treatment of breast cancer. The proposed method can be directly applied to other RNA-seq data sets for deeper disease understanding.
Destabilisation of Argonaute 2 generates a truncated protein: halfAgo2
Publisher: Sciencematters
Date: 13-11-2018
Natural Variation of the Amino-Terminal Glutamine-Rich Domain in Drosophila Argonaute2 Is Not Associated with Developmental Defects
Publisher: Public Library of Science (PLoS)
Date: 17-12-2010
Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis
Publisher: Oxford University Press (OUP)
Date: 19-10-2020
DOI: 10.1093/BIB/BBAA248
Abstract: Single-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver–Beer tool combination and the Baynorm–Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells
Publisher: Oxford University Press (OUP)
Date: 18-07-2014
DOI: 10.1093/NAR/GKU620
A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation
Publisher: Cold Spring Harbor Laboratory
Date: 13-07-2018
DOI: 10.1101/366468
Abstract: Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.
A comparative analysis of single cell small RNA sequencing data reveals heterogeneous isomiR expression and regulation
Publisher: Springer Science and Business Media LLC
Date: 18-02-2022
DOI: 10.1038/S41598-022-06876-3
Abstract: MicroRNAs (miRNAs) are non-coding small RNAs which play a critical role in the regulation of gene expression in cells. It is known that miRNAs are often expressed as multiple isoforms, called isomiRs, which may have alternative regulatory functions. Despite the recent development of several single cell small RNA sequencing protocols, these methods have not been leveraged to investigate isomiR expression and regulation to better understand their role on a single cell level. Here we integrate sequencing data from three independent studies and find substantial differences in isomiR composition that suggest that cell autonomous mechanisms may drive isomiR processing. We also find evidence of altered regulatory functions of different classes of isomiRs, when compared to their respective wild-type miRNA, which supports a biological role for many of the isomiRs that are expressed.
Detailed characterization of the posttranscriptional gene-silencing-related small RNA in a GUS gene-silenced tobacco
Publisher: Cold Spring Harbor Laboratory
Date: 10-2000
DOI: 10.1017/S1355838200001096
Abstract: Posttranscriptional gene-silencing phenomena such as cosuppression and RNA interference are associated with the occurrence of small, about 21-23 nt short RNA species homologous to the silenced gene. We here show that the small RNA present in silenced transgenic plants can easily be detected in total RNA isolated according to standard procedures. This will allow for the development of routine and early screenings for the presence of small RNA species and, therefore, gene silencing in transgenic plants. We further demonstrate that the small RNA fraction can be visualized with the SYBR Green II RNA stain, isolated from a gel, labeled and used as a specific probe. Using these approaches, we have fine-mapped the sequences of the GUS gene that are represented in the small RNA fraction of a GUS-silenced tobacco line containing an inverted repeat of the GUS gene. In this tobacco line, the silencing-associated small RNA is a mixture of fragments that cover the 3' two-thirds of the GUS coding region. The 5' coding and the 3' noncoding ends of the GUS mRNA are not represented in the small RNA fraction. The RNA fragments are not likely to be a primary synthesis product of an RNA-dependent RNA polymerase, but rather degradation products from nuclease activity. Surprisingly, RNA isolated from wild-type, untransformed plants showed the presence of a similar-sized small RNA pool. This might indicate the existence of small RNA species from putative endogenous genes that are down regulated by a similar posttranscriptional gene-silencing mechanism. The possibility of isolating and labeling the small RNA pool from wild-type plants will provide a way to identify and study such putative genes.
Cell-penetrating peptides containing the progesterone receptor polyproline domain inhibits EGF signaling and cell proliferation in lung cancer cells
Publisher: Public Library of Science (PLoS)
Date: 02-03-2022
DOI: 10.1371/JOURNAL.PONE.0264717
Abstract: Non-small cell lung cancer (NSCLC) accounts for the majority (80–85%) of all lung cancers. All current available treatments have limited efficacy. The epidermal growth factor receptor (EGFR) plays a critical role in the development and progression of NSCLC, with high EGFR expression associated with increased cell proliferation and poor prognosis. Thus, interfering with EGFR signaling has been shown to effectively reduce cell proliferation and help in the treatment of NSCLC. We previously demonstrated that the progesterone receptor (PR) contains a polyproline domain (PPD) that directly interacts with Src homology 3 (SH3) domain-containing molecules and expression of PR-PPD peptides inhibits NSCLC cell proliferation. In this study, we investigated whether the introduction of PR-PPD by cell-penetrating peptides (CPPs) could inhibit EGF-induced cell proliferation in NSCLC cells. PR-PPD was attached to a cancer-specific CPP, Buforin2 (BR2), to help deliver the PR-PPD into NSCLC cells. Interestingly, addition of BR2-2xPPD peptides containing two PR-PPD repeats was more effective in inhibiting NSCLC proliferation and significantly reduced EGF-induced phosphorylation of Erk1/2. BR2-2xPPD treatment induced cell cycle arrest by inhibiting the expression of cyclin D1 and CDK2 genes in EGFR-wild type A549 cells. Furthermore, the combination treatment of EGFR-tyrosine kinase inhibitors (TKIs), including Gefitinib or Erlotinib, with BR2-2xPPD peptides further suppressed the growth of NSCLC PC9 cells harboring EGFR mutations as compared to EGFR-TKIs treatment alone. Importantly, BR2-2xPPD peptides mediated growth inhibition in acquired Gefitinib- and Erlotinib- resistant lung adenocarcinoma cells. Our data suggests that PR-PPD is the minimal protein domain sufficient to inhibit NSCLC cell growth and has the potential to be developed as a novel NSCLC therapeutic agent.
Small RNA asymmetry in RNAi: Function in RISC assembly and gene regulation
Publisher: Wiley
Date: 20-09-2005
DOI: 10.1016/J.FEBSLET.2005.08.071
Abstract: RNAi is a conserved gene-specific regulatory mechanism, which silences target gene expression transcriptionally and post-transcriptionally. The RNAi machinery converts the sequence specific information of a long double stranded RNAs (dsRNAs) into small 21-22 nt long dsRNAs (siRNAs, miRNAs) which assemble into an effector complex, the RNA induced silencing complex (RISC). RISC assembly is asymmetric one strand of an siRNA or a miRNA preferentially incorporates into the RNA-protein complex. Here, I review the rules of the asymmetric RISC formation and discuss their possible regulatory function in several steps in RNAi.
A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-08-2001
Abstract: The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals. We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA. Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression.
Comparative molecular analysis of winter wheat cultivars and their doubled haploid derivatives
Publisher: Springer Science and Business Media LLC
Date: 03-2001
DOI: 10.1007/BF03543640
The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.BBAGRM.2016.07.013
Abstract: MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors. Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.
Evidence that siRNAs Function as Guides, Not Primers, in the Drosophila and Human RNAi Pathways
Publisher: Elsevier BV
Date: 09-2002
DOI: 10.1016/S1097-2765(02)00651-2
Abstract: In Drosophila, two features of small interfering RNA (siRNA) structure--5' phosphates and 3' hydroxyls--are reported to be essential for RNA interference (RNAi). Here, we show that as in Drosophila, a 5' phosphate is required for siRNA function in human HeLa cells. In contrast, we find no evidence in flies or humans for a role in RNAi for the siRNA 3' hydroxyl group. Our in vitro data suggest that in both flies and mammals, each siRNA guides endonucleolytic cleavage of the target RNA at a single site. We conclude that the underlying mechanism of RNAi is conserved between flies and mammals and that RNA-dependent RNA polymerases are not required for RNAi in these organisms.
Cataloguing the small RNA content of honey using next generation sequencing
Publisher: Elsevier BV
Date: 07-2021
Potato protein kinase StCPK1: A putative evolutionary link between CDPKs and CRKs
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0167-4781(98)00148-1
Abstract: Calcium-dependent protein kinases (CDPKs) in plants are characterized by a four-domain structure including conserved sequences in the catalytic domain, and in the C-terminal calmodulin-like domain. Based on this conservation we have PCR- lified and isolated a potato cDNA clone (StCPK1) from a library representing an early stage of tuber development. DNA sequence analysis revealed that in the catalytic domain, StCPK1 shares more homology with CDPK-related kinases than with CDPKs however, like CDPKs, it possesses canonical EF-hands at the calmodulin-like 3' end. StCPK1 exists in a few copies in the potato genome and is abundantly expressed in the sepals of mature flowers. Floral expression of genes homologous to StCPK1 appears to be widespread in the family Solanaceae.
Designing tangible artefacts for playful interactions and dialogues
Publisher: ACM
Date: 22-08-2007
The loop structure and the RNA helicase p72/DDX17 influence the processing efficiency of the mice miR-132
Publisher: Springer Science and Business Media LLC
Date: 07-03-2016
DOI: 10.1038/SREP22848
Abstract: miRNAs are small RNAs that are key regulators of gene expression in eukaryotic organisms. The processing of miRNAs is regulated by structural characteristics of the RNA and is also tightly controlled by auxiliary protein factors. Among them, RNA binding proteins play crucial roles to facilitate or inhibit miRNA maturation and can be controlled in a cell, tissue and species-specific manners or in response to environmental stimuli. In this study we dissect the molecular mechanism that promotes the overexpression of miR-132 in mice over its related, co-transcribed and co-regulated miRNA, miR-212. We have shown that the loop structure of miR-132 is a key determinant for its efficient processing in cells. We have also identified a range of RNA binding proteins that recognize the loop of miR-132 and influence both miR-132 and miR-212 processing. The DEAD box helicase p72/DDX17 was identified as a factor that facilitates the specific processing of miR-132.
Simultaneous compression of multiple error-corrected short-read sets for faster data transmission and better de novo assemblies.
Publisher: Oxford University Press (OUP)
Date: 14-07-2022
DOI: 10.1093/BFGP/ELAC016
Abstract: Next-Generation Sequencing has produced incredible amounts of short-reads sequence data for de novo genome assembly over the last decades. For efficient transmission of these huge datasets, high-performance compression algorithms have been intensively studied. As both the de novo assembly and error correction methods utilize the overlaps between reads data, a concern is that the will the sequencing errors bring up negative effects on genome assemblies also affect the compression of the NGS data. This work addresses two problems: how current error correction algorithms can enable the compression algorithms to make the sequence data much more compact, and whether the sequence-modified reads by the error-correction algorithms will lead to quality improvement for de novo contig assembly. As multiple sets of short reads are often produced by a single biomedical project in practice, we propose a graph-based method to reorder the files in the collection of multiple sets and then compress them simultaneously for a further compression improvement after error correction. We use ex les to illustrate that accurate error correction algorithms can significantly reduce the number of mismatched nucleotides in the reference-free compression, hence can greatly improve the compression performance. Extensive test on practical collections of multiple short-read sets does confirm that the compression performance on the error-corrected data (with unchanged size) significantly outperforms that on the original data, and that the file reordering idea contributes furthermore. The error correction on the original reads has also resulted in quality improvements of the genome assemblies, sometimes remarkably. However, it is still an open question that how to combine appropriate error correction methods with an assembly algorithm so that the assembly performance can be always significantly improved.
RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs
Publisher: MDPI AG
Date: 07-01-2020
DOI: 10.3390/CELLS9010137
Abstract: The first therapeutic nucleic acid, a DNA oligonucleotide, was approved for clinical use in 1998. Twenty years later, in 2018, the first therapeutic RNA-based oligonucleotide was United States Food and Drug Administration (FDA) approved. This promises to be a rapidly expanding market, as many emerging biopharmaceutical companies are developing RNA interference (RNAi)-based, and RNA-based antisense oligonucleotide therapies. However, miRNA therapeutics are noticeably absent. miRNAs are regulatory RNAs that regulate gene expression. In disease states, the expression of many miRNAs is measurably altered. The potential of miRNAs as therapies and therapeutic targets has long been discussed and in the context of a wide variety of infections and diseases. Despite the great number of studies identifying miRNAs as potential therapeutic targets, only a handful of miRNA-targeting drugs (mimics or inhibitors) have entered clinical trials. In this review, we will discuss whether the investment in finding potential miRNA therapeutic targets has yielded feasible and practicable results, the benefits and obstacles of miRNAs as therapeutic targets, and the potential future of the field.
A microRNA in a Multiple-Turnover RNAi Enzyme Complex
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-09-2002
Abstract: In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let - 7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Human let - 7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let - 7 –containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.
Transfer RNA-derived fragments: origins, processing, and functions
Publisher: Wiley
Date: 30-06-2011
DOI: 10.1002/WRNA.96
Abstract: Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on a recently identified group of small RNAs that are derived from transfer RNAs (tRNAs), tRNA fragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross-talk between tRFs and the canonical small RNA pathway characterized by small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). We also propose a nomenclature that is based on their processing characteristics.
Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs
Publisher: Cold Spring Harbor Laboratory
Date: 22-10-2009
DOI: 10.1261/RNA.1738409
Abstract: Deep sequencing technologies such as Illumina, SOLiD, and 454 platforms have become very powerful tools in discovering and quantifying small RNAs in erse organisms. Sequencing small RNA fractions always identifies RNAs derived from abundant RNA species such as rRNAs, tRNAs, snRNA, and snoRNA, and they are widely considered to be random degradation products. We carried out bioinformatic analysis of deep sequenced HeLa RNA and after quality filtering, identified highly abundant small RNA fragments, derived from mature tRNAs that are likely produced by specific processing rather than from random degradation. Moreover, we showed that the processing of small RNAs derived from tRNA Gln is dependent on Dicer in vivo and that Dicer cleaves the tRNA in vitro.
Principles and effects of microRNA-mediated post-transcriptional gene regulation
Publisher: Springer Science and Business Media LLC
Date: 09-10-2006
Abstract: MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.
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