A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

被引：1931

作者：

Huarte, Maite ^{[1
,2
]}

Guttman, Mitchell ^{[1
,3
]}

Feldser, David ^{[3
,4
]}

Garber, Manuel ^{[1
]}

Koziol, Magdalena J. ^{[1
,2
]}

Kenzelmann-Broz, Daniela ^{[5
,6
]}

Khalil, Ahmad M. ^{[1
,2
]}

Zuk, Or ^{[1
]}

Amit, Ido ^{[1
]}

Rabani, Michal ^{[1
]}

Attardi, Laura D. ^{[5
,6
]}

Regev, Aviv ^{[1
,3
]}

Lander, Eric S. ^{[1
,3
,7
]}

Jacks, Tyler ^{[3
,4
]}

Rinn, John L. ^{[1
,2
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA

[3] MIT, Dept Biol, Cambridge, MA 02139 USA

[4] Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[5] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[7] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA

来源：

CELL | 2010年 / 142卷 / 03期

基金：

美国国家卫生研究院;

关键词：

BINDING-SITE; TRANSCRIPTION; APOPTOSIS; PROTEINS; PATHWAY;

D O I：

10.1016/j.cell.2010.06.040

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：

Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

引用

页码：409 / 419

页数：11

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