Publication Date:
2008-05-30
Description:
With the recent recognition of non-coding RNAs (ncRNAs) flanking many genes, a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms. Here we show that an RNA-binding protein, TLS (for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB-binding protein (CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 (CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene-specific repression is directed by single-stranded, low-copy-number ncRNA transcripts tethered to the 5' regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA-binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiangting -- Arai, Shigeki -- Song, Xiaoyuan -- Reichart, Donna -- Du, Kun -- Pascual, Gabriel -- Tempst, Paul -- Rosenfeld, Michael G -- Glass, Christopher K -- Kurokawa, Riki -- CA097134/CA/NCI NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK39949/DK/NIDDK NIH HHS/ -- HL59694/HL/NHLBI NIH HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA052599-19/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL059694/HL/NHLBI NIH HHS/ -- R01 HL059694-10/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-20A1/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-26/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jul 3;454(7200):126-30. doi: 10.1038/nature06992. Epub 2008 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509338" target="_blank"〉PubMed〈/a〉
Keywords:
Allosteric Regulation
;
CREB-Binding Protein/antagonists & inhibitors/metabolism
;
Cell Line
;
Consensus Sequence
;
Cyclin D1/genetics
;
DNA Damage
;
*Down-Regulation
;
HeLa Cells
;
Histone Acetyltransferases/antagonists & inhibitors/metabolism
;
Humans
;
Oligonucleotides/genetics
;
Promoter Regions, Genetic/genetics
;
RNA, Untranslated/genetics/*metabolism
;
RNA-Binding Protein FUS/genetics/*metabolism
;
*Transcription, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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