Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements.
Cell
; 152(3): 453-66, 2013 Jan 31.
Article
en En
| MEDLINE
| ID: mdl-23374342
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 that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ribonucleoproteínas
/
Proteínas Nucleares
/
Elementos Alu
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Ribonucleoproteína Heterogénea-Nuclear Grupo C
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Transcriptoma
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido