Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription

Article

关键词: PRO-ONCOPROTEIN TLS/FUS;    NONCODING RNAS;    GENE-EXPRESSION;    COACTIVATOR;    GENOME;    TLS;    IDENTIFICATION;    CHROMATIN;    COMPLEX;    MICE;   

DOI  :  10.1038/nature06992

来源: SCIE

【 摘 要 】

With the recent recognition of non- coding RNAs ( ncRNAs) flanking many genes(1-5), a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms(6-12). 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.

【 授权许可】

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