Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins
Author(s)Wang, Eric Tzy-shi; Cody, Neal A. L.; Jog, Sonali; Biancolella, Michela; Wang, Thomas T.; Treacy, Daniel J.; Luo, Shujun; Schroth, Gary P.; Housman, David E.; Reddy, Sita; Lécuyer, Eric; Burge, Christopher B.; Wang, Thomas; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
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.
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