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PMID: 20673990 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.

Cell ·Vol. 142 ·No. 3 ·2010-08-06 ·Pages 409-19

Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL

Abstract

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.

MeSH Terms
Animals Apoptosis Down-Regulation Heterogeneous-Nuclear Ribonucleoprotein K/metabolism Humans Mice Molecular Sequence Data RNA, Untranslated/metabolism Transcription, Genetic Tumor Suppressor Protein p53/metabolism
Chemicals
Heterogeneous-Nuclear Ribonucleoprotein K RNA, Untranslated Tumor Suppressor Protein p53
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Huarte Maite
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. [email protected]
Guttman Mitchell
Feldser David
Garber Manuel
Koziol Magdalena J
Kenzelmann-Broz Daniela
Khalil Ahmad M
Zuk Or
Amit Ido
Rabani Michal
Attardi Laura D
Regev Aviv
Lander Eric S
Jacks Tyler
Rinn John L
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.06.040
Email
[email protected]
Published
2010-08-06
Pages
409-19
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2956184
Subset
IM
Grants
NCI NIH HHS · R01 CA119176 · United States
NIH HHS · DP2 OD006670 · United States
NIH HHS · DP2 OD006670-01 · United States
NCI NIH HHS · 1R01CA119176-01 · United States
NIH HHS · DP1 OD003958 · United States
Databases
GENBANK
HM210889
GEO
GSE21761
Corrections
CommentIn
PMID: 20691894
External Links
PubMed source DOI: 10.1016/j.cell.2010.06.040 PMC Full Text View journal details
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