Coevolutionary networks of splicing cis-regulatory elements

X Xiao, Z Wang, M Jang… - Proceedings of the …, 2007 - National Acad Sciences
X Xiao, Z Wang, M Jang, CB Burge
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
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 …
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.
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