Literature DB >> 20797886

The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.

Vidisha Tripathi1, Jonathan D Ellis, Zhen Shen, David Y Song, Qun Pan, Andrew T Watt, Susan M Freier, C Frank Bennett, Alok Sharma, Paula A Bubulya, Benjamin J Blencowe, Supriya G Prasanth, Kannanganattu V Prasanth.   

Abstract

Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell-type-specific AS in a concentration- and phosphorylation-dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 or overexpression of an SR protein changes the AS of a similar set of endogenous pre-mRNAs. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight the role for an nrRNA in the regulation of gene expression.
Copyright © 2010 Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 20797886      PMCID: PMC4158944          DOI: 10.1016/j.molcel.2010.08.011

Source DB:  PubMed          Journal:  Mol Cell        ISSN: 1097-2765            Impact factor:   17.970


  64 in total

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Authors:  Kannanganattu V Prasanth; Supriya G Prasanth; Zhenyu Xuan; Stephen Hearn; Susan M Freier; C Frank Bennett; Michael Q Zhang; David L Spector
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4.  Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing.

Authors:  S H Xiao; J L Manley
Journal:  Genes Dev       Date:  1997-02-01       Impact factor: 11.361

5.  Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro.

Authors:  W Cao; S F Jamison; M A Garcia-Blanco
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6.  Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity.

Authors:  J F Cáceres; T Misteli; G R Screaton; D L Spector; A R Krainer
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7.  Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2.

Authors:  S H Xiao; J L Manley
Journal:  EMBO J       Date:  1998-11-02       Impact factor: 11.598

8.  Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2/alternative splicing factor.

Authors:  Jeremy R Sanford; Jonathan D Ellis; Demian Cazalla; Javier F Cáceres
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Authors:  T Misteli; J F Cáceres; J Q Clement; A R Krainer; M F Wilkinson; D L Spector
Journal:  J Cell Biol       Date:  1998-10-19       Impact factor: 10.539

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