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- 题目:
- Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription.
- 作者:
- Wang(Xiangting),Arai(Shigeki),Song(Xiaoyuan),Reichart(Donna),Du(Kun),Pascual(Gabriel),Tempst(Paul),Rosenfeld(Michael G),Glass(Christopher K),Kurokawa(Riki)
- 状态:
- 发布时间2008-07-03 , 更新时间 2016-11-22
- 期刊:
- Nature
- 摘要:
- 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.
- 语言:
- eng
- DOI:
DataTable pData
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