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Selective constraint on human pre-mRNA splicing by protein structural properties.
Gelly J.-C., Lin H.-Y., De Brevern A. G., Chuang T.-J., Chen F.-C.
Genome Biol Evol 4, 9 (2012) 966-75 - http://www.hal.inserm.fr/inserm-00750397
Selective constraint on human pre-mRNA splicing by protein structural properties.
Jean-Christophe Gelly1, 2, Hsuan-Yu Lin3, Alexandre De Brevern () 1, 2, Trees-Juen Chuang4, Feng-Chi Chen3, 5, 6
1 :  GR-Ex, Laboratoire d'Excellence
2 :  DSIMB - Dynamique des Structures et Interactions des Macromolécules Biologiques
INSERM : U665 – INTS – Université Paris Diderot, Sorbonne Paris Cité
6 rue Alexandre Cabanel, 75739 Paris cedex 15
3 :  Institute of Population Health Sciences
National Health Research Institutes
4 :  Genomics Research Center
Academica Sinica
5 :  National Chiao-Tung University - Department of Biological Science and Technology
National Chiao-Tung University
Hsinchu, 300 Taiwan
6 :  Department of Dentistry
China Medical University
Taichung, 404 Taiwan
Alternative splicing (AS) is a major mechanism of increasing proteome diversity in complex organisms. Different AS transcript isoforms may be translated into peptide sequences of significantly different lengths and amino acid compositions. One important question, then, is how AS is constrained by protein structural requirements while peptide sequences may be significantly changed in AS events. Here, we address this issue by examining whether the intactness of three-dimensional protein structural units (compact units in protein structures, namely protein units [PUs]) tends to be preserved in AS events in human. We show that PUs tend to occur in constitutively spliced exons and to overlap constitutive exon boundaries. Furthermore, when PUs are located at the boundaries between two alternatively spliced exons (ASEs), these neighboring ASEs tend to co-occur in different transcript isoforms. In addition, such PU-spanned ASE pairs tend to have a higher frequency of being included in transcript isoforms. ASE regions that overlap with PUs also have lower nonsynonymous-to-synonymous substitution rate ratios than those that do not overlap with PUs, indicating stronger negative selection pressure in PU-overlapped ASE regions. Of note, we show that PUs have protein domain- and structural orderness-independent effects on messenger RNA (mRNA) splicing. Overall, our results suggest that fine-scale protein structural requirements have significant influences on the splicing patterns of human mRNAs.
Sciences du Vivant/Biochimie, Biologie Moléculaire
Sciences du Vivant/Génétique
Sciences du Vivant/Bio-Informatique, Biostatistique
Sciences du Vivant/Biochimie, Biologie Moléculaire/Biologie structurale

Articles dans des revues avec comité de lecture
Genome Biol Evol

protein unit – alternative splicing – protein structural constraint – protein domain – genomics – diseases – human.
Alternative Splicing – Evolution – Molecular – Exons – Gene Frequency – Humans – Protein Structure – Quaternary – Tertiary – Proteomics – RNA Precursors – RNA – Messenger – Selection – Genetic
National Health Research Institutes, Taiwan; National Science Council, Taiwan. (NSC 101-2311-B-400-003 to FCC; NSC 99-2911-I-001-017 (Programme of Integrated Actions ORCHID) and NSC99-2628-B-001-008-MY3 to TJC); Ministry of Research, France; University of Paris Diderot, Sorbonne Paris Cité, France; National Institute for Blood Transfusion (INTS), France; Institute for Health and Medical Research (INSERM), France; Partenariat Hubert Curien (PHC) Orchid for French - Taiwanese collaboration; "Investissements d'avenir", Laboratories of Excellence GR-Ex.
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