TITLE

Selective Constraint on Human Pre-mRNA Splicing by Protein Structural Properties

AUTHOR(S)
Gelly, Jean-Christophe; Lin, Hsuan-Yu; de Brevern, Alexandre G.; Chuang, Trees-Juen; Chen, Feng-Chi
PUB. DATE
September 2012
SOURCE
Genome Biology & Evolution;Sep2012, Vol. 4 Issue 9, p966
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
100353599

 

Related Articles

  • Genomic structure and cloning of two transcript isoforms of human Sp8. Milona, Maria-athina; Gough, Julie E.; Edgar, Alasdair J. // BMC Genomics;2004, Vol. 5, p86 

    Background: The Specificity proteins (Sp) are a family of transcription factors that have three highly conserved zinc-fingers located towards the carboxy-terminal that bind GC-boxes and assist in the initiation of gene transcription. Human Sp1-7 genes have been characterized. Recently, the...

  • Projection of gene-protein networks to the functional space of the proteome and its application to analysis of organism complexity. Kanapin, Alexander A.; Mulder, Nicola; Kuznetsov, Vladimir A. // BMC Genomics;2010 Supplement 1, Vol. 11, Special section p1 

    We consider the problem of biological complexity via a projection of protein-coding genes of complex organisms onto the functional space of the proteome. The latter can be defined as a set of all functions committed by proteins of an organism. Alternative splicing (AS) allows an organism to...

  • The Impact of the Nucleosome Code on Protein-Coding Sequence Evolution in Yeast. Warnecke, Tobias; Batada, Nizar N.; Hurst, Laurence D. // PLoS Genetics;Nov2008, Vol. 4 Issue 11, p1 

    Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints...

  • Cancer-associated regulation of alternative splicing. Venables, Julian P.; Klinck, Roscoe; Koh, ChuShin; Gervais-Bird, Julien; Bramard, Anne; Inkel, Lyna; Durand, Mathieu; Couture, Sonia; Froehlich, Ulrike; Lapointe, Elvy; Lucier, Jean-François; Thibault, Philippe; Rancourt, Claudine; Tremblay, Karine; Prinos, Panagiotis; Chabot, Benoit; Elela, Sherif Abou // Nature Structural & Molecular Biology;Jun2009, Vol. 16 Issue 6, p670 

    Alternative splicing of pre-mRNA increases the diversity of protein functions. Here we show that about half of all active alternative splicing events in ovarian and breast tissues are changed in tumors, and many seem to be regulated by a single factor; sequence analysis revealed binding sites...

  • Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression. SHANKARLING, Ganesh; LYNCH, Kristen W. // Biochemical Journal;7/15/2013, Vol. 453 Issue 2, p271 

    Understanding functional distinctions between related splicing regulatory proteins is critical to deciphering tissue-specific control of alternative splicing. The hnRNP (heterogeneous nuclear ribonucleoprotein) L and hnRNP LL (hnRNP L-like) proteins are paralogues that have overlapping, but...

  • Regulation of Alternative RNA Splicing by Exon Definition and Exon Sequences in Viral and Mammalian Gene Expression. Zhi-Ming Zheng // Journal of Biomedical Science;May/Jun2004, Vol. 11 Issue 3, p278 

    Intron removal from a pre-mRNA by RNA splicing was once thought to be controlled mainly by intron splicing signals. However, viral and other eukaryotic RNA exon sequences have recently been found to regulate RNA splicing, polyadenylation, export, and nonsense-mediated RNA decay in addition to...

  • Alternative splicing and RNA selection pressure — evolutionary consequences for eukaryotic genomes. Yi Xing; Lee, Christopher // Nature Reviews Genetics;Jul2006, Vol. 7 Issue 7, p499 

    Genome-wide analyses of alternative splicing have established its nearly ubiquitous role in gene regulation in many organisms. Genome sequencing and comparative genomics have made it possible to look in detail at the evolutionary history of specific alternative exons or splice sites, resulting...

  • Integrating many co-splicing networks to reconstruct splicing regulatory modules. Chao Dai; Wenyuan Li; Juan Liu; Jasmine Zhou, Xianghong // BMC Systems Biology;2012 Supplement 1, Vol. 6 Issue Suppl 1, p1 

    Background: Alternative splicing is a ubiquitous gene regulatory mechanism that dramatically increases the complexity of the protium. However, the mechanism for regulating alternative splicing is poorly understood, and study of coordinated splicing regulation has been limited to individual...

  • Computational extraction of a neural molecular network through alternative splicing. Alam, Shafiul; Huong Thi Thanh Phan; Okazaki, Mio; Takagi, Masahiro; Kawahara, Kozo; Tsukahara, Toshifumi; Suzuki, Hitoshi // BMC Research Notes;2014, Vol. 7 Issue 1, p947 

    Background Generally, the results of high throughput analyses contain information about gene expressions, and about exon expressions. Approximately 90% of primary protein-coding transcripts undergo alternative splicing in mammals. However, changes induced by alternative exons have not been...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics