2013/01/01 by Kathi Zarnack, Julian König, Mojca Tajnik +7 · 4 citations
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer #Biology #Alu element #Minigene #Transcriptome #Genetics #RNA splicing #Transposable element #Exon #Human genome #Genome #Alternative splicing #Gene #RNA #Gene expression
paper · pdf · doi:10.1016/j.cell.2012.12.023
openalex publication_date 2013/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
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.