@article{2a2ce45cc0614bb082a9c272cd8199c0,
title = "The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation",
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.",
keywords = "CELLBIO, PROTEINS, RNA",
author = "Vidisha Tripathi and Ellis, {Jonathan D.} and Zhen Shen and Song, {David Y.} and Qun Pan and Watt, {Andrew T.} and Freier, {Susan M.} and Bennett, {C. Frank} and Alok Sharma and Bubulya, {Paula A.} and Blencowe, {Benjamin J.} and Prasanth, {Supriya G.} and Prasanth, {Kannanganattu V.}",
note = "Funding Information: We would like to thank Drs. D. Bernard and A. Bessis (mouse MALAT1 plasmid); M. Carmo-Fonseca (GFP-SF1, U2AF65, U2AF35, UAP56); J. Caceres, J. Sanford, and A. Krainer (SRSF1 constructs); and R. L{\"u}hrmann (PRP6 plasmid and pAb), J. Stevenin (SRSF2 mAb), and J. Nickerson (UAP56 pAb) for their kind gift of reagents. We thank Drs. M. Hastings, A. Krainer, J. Caceres, G. Carmichael, T. Misteli, and D. Spector for the valuable discussions; J. Sanford for sharing SRSF1 CLIP-seq data; and J. Kim, Y. Ge, and R. Zheng for technical help. We also would like to thank Drs. N. Akimitsu, M. Bellini, A. Lal, P. Newmark, and Prasanth lab members for critical reading of the manuscript. This work was supported by a grant UIUC-ICR-MCB (to K.V.P.) and grant NSF0843604 (to S.G.P.). A.T.W., S.M.F., and C.F.B. are employees of Isis Pharmaceutical Corp. They receive salary from the company and hold stock options. ",
year = "2010",
month = sep,
doi = "10.1016/j.molcel.2010.08.011",
language = "English (US)",
volume = "39",
pages = "925--938",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}