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PMID: 17998536 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Coevolutionary networks of splicing cis-regulatory elements.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 47 ·2007-11-20 ·Pages 18583-8

Xiao X, Wang Z, Jang M, Burge CB

Abstract

Accurate and efficient splicing of eukaryotic pre-mRNAs requires recognition by trans-acting factors of a complex array of cis-acting RNA elements. Here, we developed a generalized Bayesian network to model the coevolution of splicing cis elements in diverse eukaryotic taxa. Cross-exon but not cross-intron compensatory interactions between the 5' splice site (5'ss) and 3' splice site (3'ss) were observed in human/mouse, indicating that the exon is the primary evolutionary unit in mammals. Studied plants, fungi, and invertebrates exhibited exclusively cross-intron interactions, suggesting that intron definition drives evolution in these organisms. In mammals, 5'ss strength and the strength of several classes of exonic splicing silencers (ESSs) evolved in a correlated way, whereas specific exonic splicing enhancers (ESEs), including motifs associated with hTra2, SRp55, and SRp20, evolved in a compensatory manner relative to the 5'ss and 3'ss. Interactions between specific ESS or ESE motifs were not observed, suggesting that elements bound by different factors are not commonly interchangeable. Thus, the splicing elements defining exons coevolve in a way that preserves overall exon strength, allowing specific elements to substitute for loss or weakening of others.

MeSH Terms
Animals Binding Sites Biological Evolution Exons/genetics Humans Introns/genetics Models, Genetic Mutation/genetics RNA Splice Sites/genetics Regulatory Elements, Transcriptional/genetics
Chemicals
RNA Splice Sites
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Xiao Xinshu
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Wang Zefeng
Jang Minyoung
Burge Christopher B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0707349104
Published
2007-11-20
Epub
2007-00-12
Pages
18583-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2141820
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0707349104 PMC Full Text View journal details
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