Global identification of hnRNP A1 binding sites for SSO-based splicing modulation.

ABSTRACT:

Background

Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known.

Results

Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif. We find that hnRNP A1 binding in proximal introns may be important for repressing exons. We show that i

SUBMITTER: Bruun GH 

PROVIDER: S-EPMC4932749 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature