The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation

被引：1951

作者：

Tripathi, Vidisha ^{[1
]}

Ellis, Jonathan D. ^{[2
,3
]}

Shen, Zhen ^{[1
]}

Song, David Y. ^{[1
]}

Pan, Qun ^{[2
,3
]}

Watt, Andrew T. ^{[4
]}

Freier, Susan M. ^{[4
]}

Bennett, C. Frank ^{[4
]}

Sharma, Alok ^{[5
]}

Bubulya, Paula A. ^{[5
]}

Blencowe, Benjamin J. ^{[2
,3
]}

Prasanth, Supriya G. ^{[1
]}

Prasanth, Kannanganattu V. ^{[1
]}

机构：

[1] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA

[2] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[3] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada

[4] ISIS Pharmaceut, Carlsbad, CA 92008 USA

[5] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA

来源：

MOLECULAR CELL | 2010年 / 39卷 / 06期

基金：

美国国家科学基金会;

关键词：

GENE-EXPRESSION; PROTEIN-PROTEIN; FACTOR SF2/ASF; RS DOMAIN; DEPHOSPHORYLATION; INSIGHTS; TRANSCRIPTION; SPECIFICITY; COMPLEXITY; RETENTION;

D O I：

10.1016/j.molcel.2010.08.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-typespecific 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.

引用

页码：925 / 938

页数：14

共 60 条

[1] The eukaryotic genome as an RNA machine
Amaral, Paulo P.
Dinger, Marcel E.
Mercer, Tim R.
Mattick, John S.
[J]. SCIENCE, 2008, 319 (5871) : 1787 - 1789
[2] Alternative splicing: New insights from global analyses
Blencowe, Benjamin J.
[J]. CELL, 2006, 126 (01) : 37 - 47
[3] Broad specificity of SR (serine/arginine) proteins in the regulation of alternative splicing of pre-messenger RNA
Bourgeois, CF
Lejeune, F
Stévenin, J
[J]. PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 78, 2004, 78 : 37 - 88
[4] FUNCTIONAL-ANALYSIS OF PREMESSENGER RNA SPLICING FACTOR SF2/ASF STRUCTURAL DOMAINS
CACERES, JF
KRAINER, AR
[J]. EMBO JOURNAL, 1993, 12 (12) : 4715 - 4726
[5] Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity
Caceres, JF
Misteli, T
Screaton, GR
Spector, DL
Krainer, AR
[J]. JOURNAL OF CELL BIOLOGY, 1997, 138 (02) : 225 - 238
[6] Global analysis of alternative splicing differences between humans and chimpanzees
Calarco, John A.
Xing, Yi
Caceres, Mario
Calarco, Joseph P.
Xiao, Xinshu
Pan, Qun
Lee, Christopher
Preuss, Todd M.
Blencowe, Benjamin J.
[J]. GENES & DEVELOPMENT, 2007, 21 (22) : 2963 - 2975
[7] Cao WH, 1997, RNA, V3, P1456
[8] Origins and Mechanisms of miRNAs and siRNAs
Carthew, Richard W.
Sontheimer, Erik J.
[J]. CELL, 2009, 136 (04) : 642 - 655
[9] Nuclear export and retention signals in the RS domain of SR proteins
Cazalla, D
Zhu, J
Manche, L
Huber, E
Krainer, AR
Cáceres, JF
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (19) : 6871 - 6882
[10] Altered Nuclear Retention of mRNAs Containing Inverted Repeats in Human Embryonic Stem Cells: Functional Role of a Nuclear Noncoding RNA
Chen, Ling-Ling
Carmichael, Gordon G.
[J]. MOLECULAR CELL, 2009, 35 (04) : 467 - 478

← 1 2 3 4 5 6 →