Transcriptome-wide Regulation of Pre-mRNA Splicing and MRNA Localization by Muscleblind Proteins

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Aug 21

PMID 22901804

Citations 307

Authors

Eric T Wang

Neal A L Cody

Sonali Jog

Michela Biancolella

Thomas T Wang

Daniel J Treacy

Shujun Luo

Gary P Schroth

David E Housman

Sita Reddy

Eric Lecuyer

Christopher B Burge

Affiliations

Soon will be listed here.

Abstract

The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of subcellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs in both mouse and Drosophila cells, and Mbnl-dependent translation and protein secretion were observed for a subset of mRNAs with Mbnl-dependent localization. These findings hold several new implications for DM pathogenesis.

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