CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.

Scientific Reports
Akio MasudaKinji Ohno

Abstract

CUGBP1 and MBNL1 are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. We globally determined the in vivo RNA-binding sites of CUGBP1 and MBNL1. Interestingly, CUGBP1 and MBNL1 are both preferentially bound to 39 UTRs. Analysis of CUGBP1- and MBNL1-bound 39 UTRs demonstrated that both factors mediate accelerated mRNA decay and temporal profiles of expression arrays supported this. Role of CUGBP1 on accelerated mRNA decay has been previously reported, but the similar function of MBNL1 has not been reported to date. It is well established that CUGBP1 and MBNL1 regulate alternative splicing. Screening by exon array and validation by RT-PCR revealed position dependence of CUGBP1- and MBNL1-binding sites on the resulting alternative splicing pattern. This study suggests that regulation of CUGBP1 and MBNL1 is essential for accurate control of destabilization of a broad spectrum of mRNAs as well as of alternative splicing events.

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Datasets Mentioned

BETA
GSE29990
GSE27583
ERP000789

Methods Mentioned

BETA
HITS-CLIP
CLIP
PCR
transfection
MBNL1-CLIP
chips
Assay

Software Mentioned

Perl
ImageJ
BWA 50
BEDTools
MEME
ENSEMBL
ArrayExpress
SeqMonk
Affymetrix Expression Console
Multiple EM for Motif Elicitation ( MEME )

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