The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.
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.
Tripathi
Vidisha
V
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Ellis
Jonathan D
JD
Shen
Zhen
Z
Song
David Y
DY
Pan
Qun
Q
Watt
Andrew T
AT
Freier
Susan M
SM
Bennett
C Frank
CF
Sharma
Alok
A
Bubulya
Paula A
PA
Blencowe
Benjamin J
BJ
Prasanth
Supriya G
SG
Prasanth
Kannanganattu V
KV
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D012322:RNA Precursors / Q000378:metabolism; D000072260:RNA Splicing Factors; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C408605:PRPF6 protein, human; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; C088203:SON protein, human; D014157:Transcription Factors; D000068103:Serine-Arginine Splicing Factors
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