ORCID Profile
0000-0001-8249-358X
Current Organisation
University of California, Berkeley
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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.
Gene Expression (incl. Microarray and other genome-wide approaches) | Genomics | Bioinformatics | Genetics
Inherited Diseases (incl. Gene Therapy) | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences |
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.BBRC.2007.04.152
Abstract: The 5'-untranslated region (5'-UTR) of RNA of tobacco mosaic virus (TMV), called omega sequence, is known as an mRNA leader promoting efficient initiation of translation. The central part of the sequence consists of many CAA repeats, which were reported to be mainly responsible for the enhancing activity of the omega leader. In this work we synthesized the polyribonucleotides containing either the natural omega sequence or the regular (CAA)(n) sequence, and studied them using UV spectrophotometry and analytical ultracentrifugation methods. It was demonstrated that the polyribonucleotides manifest significant hypochromicity, cooperative melting of their structures upon heating, high melting temperature, and the sedimentation coefficients typical of compactly folded RNAs of this size. Thus, the omega leader and its core (CAA)(n) repeat sequence devoid of secondary structure of the Watson-Crick type seem to be well structured elements of mRNA.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Springer Science and Business Media LLC
Date: 26-05-2014
Publisher: Informa UK Limited
Date: 25-02-2022
Publisher: Cold Spring Harbor Laboratory
Date: 16-03-2022
DOI: 10.1101/2022.03.14.484124
Abstract: The epitranscriptome embodies many new and largely unexplored functions of RNA. A major roadblock in the epitranscriptomics field is the lack of transcriptome-wide methods to detect more than a single RNA modification type at a time, identify RNA modifications in in idual molecules, and estimate modification stoichiometry accurately. We address these issues with CHEUI (CH3 (methylation) Estimation Using Ionic current), a new method that concurrently detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) in in idual RNA molecules from the same s le, as well as differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals with convolutional neural networks to achieve high single-molecule accuracy and outperforms other methods in detecting m6A and m5C sites and quantifying their stoichiometry. CHEUI’s unique capability to identify two modification types in the same s le reveals a non-random co-occurrence of m6A and m5C in mRNA transcripts in cell lines and tissues. CHEUI unlocks an unprecedented potential to study RNA modification configurations and discover new epitranscriptome functions.
Publisher: Wiley
Date: 14-06-2018
DOI: 10.1002/WRNA.1490
Abstract: The cover image, by Nikolay E. Shirokikh and Thomas Preiss, is based on the Overview Translation initiation by capdependent ribosome recruitment: Recent insights and open questions , DOI: 10.1002/wrna.1473 . Image Credit: Dr. Cheryl Li, The Babraham Institute. image
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 12-2022
Publisher: Cold Spring Harbor Laboratory
Date: 24-09-2022
DOI: 10.1101/2022.09.23.509222
Abstract: Long-read sequencing enables isoform-resolved detection of functionally important RNA elements, such as RNA chemical modifications, RNA secondary structure, or RNA-protein interaction sites. Importantly, the functional impact of these elements can relate to their positions relative to isoform-specific transcript features, such as start and stop codons, open reading frames, exon-exon junctions and transcript termini. Relating transcriptomic and genomic features during sequencing data analysis is challenged by the flexibility of RNA biogenesis and the ersity of alternative mRNA transcripts. To address these challenges and streamline the mapping between transcriptome-mapped data and genome-mapped data, we developed R2Dtool. We illustrate R2Dtool’s capability to process long-read transcriptomic information and potential for interpretation in the context of transcript and genomic annotation features using epitranscriptomics data. R2Dtool embraces and expedites analysis of RNA complexity, and we anticipate it will empower multiple transcriptomic studies for interpretation and discovery. R2Dtool is freely available under the MIT license from omprna/R2Dtool .
Publisher: Cold Spring Harbor Laboratory
Date: 14-03-2022
DOI: 10.1101/2022.03.13.483370
Abstract: Full-transcriptome methods have brought versatile power to protein biosynthesis research, but remain difficult to apply for the quantification of absolute protein synthesis rates. Here we propose and, using modified translation complex profiling, confirm co-localisation of ribosomes on messenger(m)RNA resulting from their diffusional dynamics. We demonstrate that these stochastically co-localised ribosomes are linked with the translation initiation rate and provide a robust variable to model and quantify specific protein output from mRNA.
Publisher: Informa UK Limited
Date: 04-03-2015
Publisher: Cold Spring Harbor Laboratory
Date: 20-10-2022
DOI: 10.1101/2022.10.19.512968
Abstract: Algorithms developed for basecalling Nanopore signals have primarily focused on DNA to date and utilise the raw signal as the only input. However, it is known that messenger RNA (mRNA), which dominates Nanopore direct RNA (dRNA) sequencing libraries, contains specific nucleotide patterns that are implicitly encoded in the Nanopore signals since RNA is always sequenced from the 3’ to 5’ direction. In this study we present an approach to exploit the sequence biases in mRNA as an additional input to dRNA basecalling. We developed a probabilistic model of mRNA language and propose a modified CTC beam search decoding algorithm to conditionally incorporate the language model during basecalling. Our findings demonstrate that inclusion of mRNA language is able to guide CTC beam search decoding towards the more probable nucleotide sequence. We also propose a time efficient approach to decoding variable length nanopore signals. This work provides the first demonstration of the potential for biological language to inform Nanopore basecalling. Code is available at: omprna/radian .
Publisher: Springer Science and Business Media LLC
Date: 14-02-2019
DOI: 10.1038/S41598-018-37037-0
Abstract: Circular RNAs (circRNAs) exhibit unique properties due to their covalently closed nature. Models of circRNAs synthesis and function are emerging but much remains undefined about this surprisingly prevalent class of RNA. Here, we identified exonic circRNAs from human and mouse RNA-sequencing datasets, documenting multiple new ex les. Addressing function, we found that many circRNAs co-sediment with ribosomes, indicative of their translation potential. By contrast, circRNAs with potential to act as microRNA sponges were scarce, with some support for a collective sponge function by groups of circRNAs. Addressing circRNA biogenesis, we delineated several features commonly associated with circRNA occurrence. CircRNA-producing genes tend to be longer and to contain more exons than average. Back-splice acceptor exons are strongly enriched at ordinal position 2 within genes, and circRNAs typically have a short exon span with two exons being the most prevalent. The flanking introns either side of circRNA loci are exceptionally long. Of note also, single-exon circRNAs derive from unusually long exons while multi-exon circRNAs are mostly generated from exons of regular length. These findings independently validate and extend similar observations made in a number of prior studies. Furthermore, we analysed high-resolution RNA polymerase II occupancy data from two separate human cell lines to reveal distinctive transcription dynamics at circRNA-producing genes. Specifically, RNA polymerase II traverses the introns of these genes at above average speed concomitant with an accentuated slow-down at exons. Collectively, these features indicate how a perturbed balance between transcription and linear splicing creates important preconditions for circRNA production. We speculate that these preconditions need to be in place so that looping interactions between flanking introns can promote back-splicing to raise circRNA production to appreciable levels.
Publisher: Wiley
Date: 04-2015
DOI: 10.1002/0471142905.HG1115S85
Abstract: Most applications for RNA‐seq require the depletion of abundant transcripts to gain greater coverage of the underlying transcriptome. The sequences to be targeted for depletion depend on application and species and in many cases may not be supported by commercial depletion kits. This unit describes a method for generating RNA‐seq libraries that incorporates probe‐directed degradation (PDD), which can deplete any unwanted sequence set, with the low‐bias split‐adapter method of library generation (although many other library generation methods are in principle compatible). The overall strategy is suitable for applications requiring customized sequence depletion or where faithful representation of fragment ends and lack of sequence bias is paramount. We provide guidelines to rapidly design specific probes against the target sequence, and a detailed protocol for library generation using the split‐adapter method including several strategies for streamlining the technique and reducing adapter dimer content. © 2015 by John Wiley & Sons, Inc.
Publisher: Wiley
Date: 06-04-2018
DOI: 10.1002/WRNA.1473
Abstract: Gene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple types of regulatory intervention. The “consensus” model, featuring cap‐dependent ribosome entry and scanning of mRNA leader sequences, represents the predominantly utilized initiation pathway across eukaryotes, although several variations of the model and alternative initiation mechanisms are also known. Recent advances in structural biology techniques have enabled remarkable molecular‐level insights into the functional states of eukaryotic ribosomes, including a range of ribosomal complexes with different combinations of translation initiation factors that are thought to represent bona fide intermediates of the initiation process. Similarly, high‐throughput sequencing‐based ribosome profiling or “footprinting” approaches have allowed much progress in understanding the elongation phase of translation, and variants of them are beginning to reveal the remaining mysteries of initiation, as well as aspects of translation termination and ribosomal recycling. A current view on the eukaryotic initiation mechanism is presented here with an emphasis on how recent structural and footprinting results underpin axioms of the consensus model. Along the way, we further outline some contested mechanistic issues and major open questions still to be addressed. This article is categorized under: Translation Translation Mechanisms Translation Translation Regulation RNA Interactions with Proteins and Other Molecules Protein–RNA Interactions: Functional Implications
Publisher: Springer Science and Business Media LLC
Date: 20-07-2016
DOI: 10.1038/NATURE18647
Abstract: Regulation of messenger RNA translation is central to eukaryotic gene expression control. Regulatory inputs are specified by them RNA untranslated regions (UTRs) and often target translation initiation. Initiation involves binding of the 40S ribosomal small subunit (SSU) and associated eukaryotic initiation factors (eIFs)near the mRNA 5′ cap the SSU then scans in the 3′ direction until it detects the start codon and is joined by the 60S ribosomal large subunit (LSU) to form the 80S ribosome. Scanning and other dynamic aspects of the initiation model have remained as conjectures because methods to trap early intermediates were lacking. Here we uncover the dynamics of the complete translation cycle in live yeast cells using translation complex profile sequencing (TCP-seq), a method developed from the ribosome profiling approach. We document scanning by observing SSU footprints along 5′ UTRs. Scanning SSU have 5′-extended footprints (up to~75 nucleotides), indicative of additional interactions with mRNA emerging from the exit channel, promoting forward movement. We visualized changes in initiation complex conformation as SSU footprints coalesced into three major sizes at start codons (19, 29 and 37 nucleotides). These share the same 5′ start site but differ at the 3′ end, reflecting successive changes at the entry channel from an open to a closed state following start codon recognition. We also observe SSU 'lingering' at stop codons after LSU departure. Our results underpin mechanistic models of translation initiation and termination, built on decades of biochemical and structural investigation, with direct genome-wide in vivo evidence. Our approach captures ribosomal complexes at all phases of translation and will aid in studying translation dynamics in erse cellular contexts. Dysregulation of translation is common in disease and, for ex le, SSU scanning is a target of anti-cancer drug development. TCP-seq will prove useful in discerning differences in mRNA-specific initiation in pathologies and their response to treatment.
Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2022
DOI: 10.1101/2022.11.29.518281
Abstract: We present the first biochemical-free technology for Real-time In Silico Enrichment of RNA species (RISER). RISER classifies RNA species from direct RNA nanopore signals, without the need for basecalling or a reference, and communicates with the sequencing hardware in real-time to enact in silico targeted RNA sequencing. We illustrate RISER for the enrichment and depletion of coding and non-coding RNA, demonstrating a 3.4-3.6x enrichment and 6.2-6.7x depletion of non-coding RNA in live sequencing experiments.
Location: United States of America
Start Date: 2018
End Date: 12-2021
Amount: $471,552.00
Funder: Australian Research Council
View Funded Activity