Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins
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Burge_Transcriptome-wide.pdf
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Author(s)
Cody, Neal A. L.
Jog, Sonali
Biancolella, Michela
Wang, Thomas T.
Treacy, Daniel J.
Luo, Shujun
Schroth, Gary P.
Reddy, Sita
Lécuyer, Eric
Wang, Thomas
Date Issued
August 2012
Journal
Cell
Publisher
Elsevier B.V.
Citation
Wang, Eric T., Neal A.L. Cody, Sonali Jog, Michela Biancolella, Thomas T. Wang, Daniel J. Treacy, Shujun Luo, et al. “Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins.” Cell 150, no. 4 (August 2012): 710-724. © 2012 Elsevier Inc.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.cell.2012.06.041
