ORCID Profile
0000-0002-8209-173X
Current Organisation
CNRS
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Publisher: Cold Spring Harbor Laboratory
Date: 05-2022
DOI: 10.1101/2022.04.30.490124
Abstract: Amino acids evolve at different speeds within protein sequences, because their functional and structural roles are different. However, the position of an amino-acid within the sequence is not known to influence this evolutionary speed. Here we discovered that amino-acid evolve almost twice faster at protein termini than in their centre, hinting at a strong topological bias along the sequence length. We further show that the distribution of functional domains and of solvent-accessible residues in proteins readily explain how functional constrains are weaker at their termini, leading to the observed excess of amino-acid substitutions. Finally, we show that methods inferring sites under positive selection are strongly biased towards protein termini, suggesting that they may confound positive selection with weak negative selection. These results suggest that accounting for positional information should improve evolutionary models.
Publisher: eLife Sciences Publications, Ltd
Date: 19-12-2019
DOI: 10.7554/ELIFE.49708
Abstract: mRNA translation and decay appear often intimately linked although the rules of this interplay are poorly understood. In this study, we combined our recent P-body transcriptome with transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors, and with available CLIP and related data. This revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA stability: P-bodies contain mostly AU-rich mRNAs, which have a particular codon usage associated with a low protein yield AU-rich and GC-rich transcripts tend to follow distinct decay pathways and the targets of sequence-specific RBPs and miRNAs are also biased in terms of GC content. Altogether, these results suggest an integrated view of post-transcriptional control in human cells where most translation regulation is dedicated to inefficiently translated AU-rich mRNAs, whereas control at the level of 5’ decay applies to optimally translated GC-rich mRNAs.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.YMETH.2013.03.022
Abstract: An emergent strategy for the transcriptome-wide study of protein-RNA interactions is CLIP-seq (crosslinking and immunoprecipitation followed by high-throughput sequencing). We combined CLIP-seq and mRNA-seq to identify direct RNA binding sites of eIF4AIII in human cells. This RNA helicase is a core constituant of the Exon Junction Complex (EJC), a multifunctional protein complex associated with spliced mRNAs in metazoans. Here, we describe the successive steps of the CLIP protocol and the computational tools and strategies we employed to map the physiological targets of eIF4AIII on human RNAs.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2012
DOI: 10.1038/NSMB.2420
Abstract: The exon junction complex (EJC) is a central effector of the fate of mRNAs, linking nuclear processing to mRNA transport, translation and surveillance. However, little is known about its transcriptome-wide targets. We used cross-linking and immunoprecipitation methods coupled to high-throughput sequencing (CLIP-seq) in human cells to identify the binding sites of the DEAD-box helicase eIF4AIII, an EJC core component. CLIP reads form peaks that are located mainly in spliced mRNAs. Most expressed exons harbor peaks either in the canonical EJC region, located ~24 nucleotides upstream of exonic junctions, or in other noncanonical regions. Notably, both of these types of peaks are preferentially associated with unstructured and purine-rich sequences containing the motif GAAGA, which is a potential binding site for EJC-associated factors. Therefore, EJC positions vary spatially and quantitatively between exons. This transcriptome-wide mapping of human eIF4AIII reveals unanticipated aspects of the EJC and broadens its potential impact on post-transcriptional regulation.
Publisher: eLife Sciences Publications, Ltd
Date: 12-2019
Publisher: Oxford University Press (OUP)
Date: 28-02-2023
Abstract: Amino acids evolve at different speeds within protein sequences, because their functional and structural roles are different. Notably, amino acids located at the surface of proteins are known to evolve more rapidly than those in the core. In particular, amino acids at the N- and C-termini of protein sequences are likely to be more exposed than those at the core of the folded protein due to their location in the peptidic chain, and they are known to be less structured. Because of these reasons, we would expect that amino acids located at protein termini would evolve faster than residues located inside the chain. Here we test this hypothesis and found that amino acids evolve almost twice as fast at protein termini compared with those in the center, hinting at a strong topological bias along the sequence length. We further show that the distribution of solvent-accessible residues and functional domains in proteins readily explain how structural and functional constraints are weaker at their termini, leading to the observed excess of amino acid substitutions. Finally, we show that the specific evolutionary rates at protein termini may have direct consequences, notably misleading in silico methods used to infer sites under positive selection within genes. These results suggest that accounting for positional information should improve evolutionary models.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2018
Publisher: Cold Spring Harbor Laboratory
Date: 21-08-2002
DOI: 10.1101/GR.222402
Abstract: The freshwater pufferfish Tetraodon nigroviridis (TNI) has become highly attractive as a compact reference vertebrate genome for gene finding and validation. We have mapped genes, which are more or less evenly spaced on the human chromosomes 9 and X, on Tetraodon chromosomes using fluorescence in situ hybridization (FISH), to establish syntenic relationships between Tetraodon and other key vertebrate genomes. PufferFISH revealed that the human X is an orthologous mosaic of three Tetraodon chromosomes. More than 350 million years ago, an ancestral vertebrate autosome shared orthologous Xp and Xq genes with Tetraodon chromosomes 1 and 7. The shuffled order of Xp and Xq orthologs on their syntenic Tetraodon chromosomes can be explained by the prevalence of evolutionary inversions. The Tetraodon 2 orthologous genes are clustered in human Xp11 and represent a recent addition to the eutherian X sex chromosome. The human chromosome 9 and the avian Z sex chromosome show a much lower degree of synteny conservation in the pufferfish than the human X chromosome. We propose that a special selection process during vertebrate evolution has shaped a highly conserved array(s) of X-linked genes long before the X was used as a mammalian sex chromosome and many X chromosomal genes were recruited for reproduction and/or the development of cognitive abilities. [Sequence data reported in this paper have been deposited in GenBank and assigned the following accession no: AJ308098 .]
No related grants have been discovered for Hugues ROEST CROLLIUS.