Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins
Open accessAbstract
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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Dual functions for splicing regulators in 3'-end poly-A site selection and mRNA transport have been described.
“Indeed, dual functions for splicing regulators in 3′-end poly-A site selection and mRNA transport have been described26,27”
From A compendium of RNA-binding motifs for decoding gene regulation (2013) · cites this paper as [27]
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- Authors
- Wang, E. T., Cody, N. A. L., Jog, S., Biancolella, M., Wang, T. T., Treacy, D. J., Luo, S., Schroth, G. P., Housman, D. E., Reddy, S., Lécuyer, E., & Burge, C. B.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Montreal Clinical Research Institute (CA)
- University of Southern California (US)
- Massachusetts Institute of Technology (US)
- Illumina (United States) (US)
- Corresponding author
- Burge, Christopher B.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 150
- Issue
- 4
- Pages
- 710-724
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3428802
- OpenAlex
- W2013963839
- Cited by
- 490
- References
- 72
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- FWCI
- 18.76
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- journal article
- Language
- en
- Open access
- bronze
- doi.org
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- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Human Genome Research Institute (RC2HG005624, R01HG002439)
- National Institute of General Medical Sciences (R01GM085319)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- muscleblind-like proteins, MBNL1, MBNL2, RNA-binding proteins, pre-mRNA splicing, mRNA localization, myotonic dystrophy, CUG repeat expansion, 3' splice site, 5' splice site, CLIP-seq, translation (biology), protein secretion, Drosophila, mice
- MeSH terms
- Animals, DNA-Binding Proteins, Drosophila melanogaster, Exons, Mice, Inbred C57BL, Myotonic Dystrophy, Nuclear Proteins, Organ Specificity, RNA Splicing, RNA, Messenger, RNA-Binding Proteins, 3' Untranslated Regions, RNA Splice Sites, Drosophila Proteins, Myoblasts, Mice, Mice, 129 Strain, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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