Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription Journal Article
| Authors: | Wang, X.; Arai, S.; Song, X.; Reichart, D.; Du, K.; Pascual, G.; Tempst, P.; Rosenfeld, M. G.; Glass, C. K.; Kurokawa, R. |
| Article Title: | Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription |
| Abstract: | 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. ©2008 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | signal transduction; controlled study; human cell; dna damage; gene targeting; cell line; protein; down-regulation; genetic transcription; protein interaction; transcription, genetic; enzyme activity; hela cells; rna binding protein; rna; dna; gene repression; dna flanking region; rna, untranslated; cyclin d1; rna binding; gene location; protein modification; oligonucleotides; cyclic amp responsive element binding protein; allosteric regulation; allosterism; inhibition; rna-binding protein fus; protein p300; consensus sequence; single stranded rna; promoter regions (genetics); histone acetyltransferase; 3 (3 cyclopentyloxy 4 methoxybenzyl) 6 ethylamino 8 isopropyl 3h purine; protein tls; creb-binding protein; histone acetyltransferases |
| Journal Title: | Nature |
| Volume: | 454 |
| Issue: | 7200 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-07-03 |
| Start Page: | 126 |
| End Page: | 130 |
| Language: | English |
| DOI: | 10.1038/nature06992 |
| PUBMED: | 18509338 |
| PROVIDER: | scopus |
| PMCID: | PMC2823488 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 132" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus" |
