Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements.

ABSTRACT: There are ~650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements th

SUBMITTER: Zarnack K 

PROVIDER: S-EPMC3629564 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature