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PMID: 20797886 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Molecular cell ·Vol. 39 ·No. 6 ·2010-09-24 ·Pages 925-38

Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV

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.

MeSH Terms
Alternative Splicing/genetics Animals Binding Sites/genetics Cell Line Cell Nucleus/genetics,pathology DNA-Binding Proteins/genetics,metabolism HeLa Cells Humans Intranuclear Space/metabolism Mice Minor Histocompatibility Antigens Mitosis/genetics Nuclear Proteins/genetics,metabolism Phosphorylation/physiology Protein Binding/physiology Protein Interaction Domains and Motifs/genetics RNA Precursors/metabolism RNA Splicing Factors RNA, Untranslated/genetics,physiology RNA-Binding Proteins/genetics,metabolism Regulatory Sequences, Ribonucleic Acid/genetics Serine-Arginine Splicing Factors Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Minor Histocompatibility Antigens Nuclear Proteins PRPF6 protein, human RNA Precursors RNA Splicing Factors RNA, Untranslated RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid SON protein, human Transcription Factors Serine-Arginine Splicing Factors
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Tripathi Vidisha
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Ellis Jonathan D
Shen Zhen
Song David Y
Pan Qun
Watt Andrew T
Freier Susan M
Bennett C Frank
Sharma Alok
Bubulya Paula A
Blencowe Benjamin J
Prasanth Supriya G
Prasanth Kannanganattu V
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.08.011
Published
2010-09-24
Pages
925-38
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC4158944
Subset
IM
Grants
NIGMS NIH HHS · R15 GM084407 · United States
Corrections
CommentIn
PMID: 20864030
External Links
PubMed source DOI: 10.1016/j.molcel.2010.08.011 PMC Full Text View journal details
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