Differential GC Content between Exons and Introns Establishes Distinct Strategies of Splice-Site Recognition

Maayan Amit, Maya Donyo, Dror Hollander, Amir Goren, Eddo Kim, Sahar Gelfman, Galit Lev-Maor, David Burstein, Schraga Schwartz, Benny Postolsky, Tal Pupko, Gil Ast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

During evolution segments of homeothermic genomes underwent a GC content increase. Our analyses reveal that two exon-intron architectures have evolved from an ancestral state of low GC content exons flanked by short introns with a lower GC content. One group underwent a GC content elevation that abolished the differential exon-intron GC content, with introns remaining short. The other group retained the overall low GC content as well as the differential exon-intron GC content, and is associated with longer introns. We show that differential exon-intron GC content regulates exon inclusion level in this group, in which disease-associated mutations often lead to exon skipping. This group@s exons also display higher nucleosome occupancy compared to flanking introns and exons of the other group, thus " marking" them for spliceosomal recognition. Collectively, our results reveal that differential exon-intron GC content is a previously unidentified determinant of exon selection and argue that the two GC content architectures reflect the two mechanisms by which splicing signals are recognized: exon definition and intron definition.

Original languageEnglish
Pages (from-to)543-556
Number of pages14
JournalCell Reports
Volume1
Issue number5
DOIs
StatePublished - 31 May 2012

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