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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alternative Splicing / genetics*
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Animals
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Binding Sites / genetics
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Cell Line
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Cell Nucleus / genetics
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Cell Nucleus / pathology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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HeLa Cells
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Humans
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Intranuclear Space / metabolism
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Mice
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Minor Histocompatibility Antigens
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Mitosis / genetics
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation / physiology
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Protein Binding / physiology
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Protein Interaction Domains and Motifs / genetics
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RNA Precursors / metabolism
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RNA Splicing Factors
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RNA, Untranslated / genetics
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RNA, Untranslated / physiology*
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Regulatory Sequences, Ribonucleic Acid / genetics
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Serine-Arginine Splicing Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Minor Histocompatibility Antigens
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Nuclear Proteins
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PRPF6 protein, human
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RNA Precursors
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RNA Splicing Factors
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RNA, Untranslated
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RNA-Binding Proteins
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Regulatory Sequences, Ribonucleic Acid
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SON protein, human
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Transcription Factors
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Serine-Arginine Splicing Factors