Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII.
Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII.
复制标题
DOI：
10.1016/j.cell.2012.08.004
复制
发表时间：
2012-09-14
期刊：
影响因子：
64.5
通讯作者：
Kiernan R
中科院分区：
文献类型：
--
作者：
Wagschal A;Rousset E;Basavarajaiah P;Contreras X;Harwig A;Laurent-Chabalier S;Nakamura M;Chen X;Zhang K;Meziane O;Boyer F;Parrinello H;Berkhout B;Terzian C;Benkirane M;Kiernan R
转录延伸日益被认为是基因调控的一种重要机制。在此，我们表明微处理器以一种不依赖RNA干扰（RNAi）的方式控制基因表达。微处理器协调终止因子Setx和Xrn2以及3′ - 5′外切核糖核酸酶Rrp6的募集，通过切割茎环RNA（TAR）在HIV - 1启动子处引发RNA聚合酶II（RNAPII）暂停和过早终止。Rrp6进一步加工切割产物，产生一种小RNA，这种小RNA是介导HIV - 1启动子处有效的转录抑制和染色质重塑所必需的。利用染色质免疫沉淀结合高通量测序（ChIP - seq），我们确定了其转录受微处理器调节的细胞基因靶点。我们的研究揭示了由核糖核酸酶Drosha/Dgcr8、Xrn2和Rrp6的协同活性介导的RNAPII暂停和过早终止，作为一种依赖RNAPII的转录延伸的调控机制。
Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3′–5′ exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation.
登录
查看更多内容
影响因子：
64.5
作者：
Kim KY;Levin DE
通讯作者：
Levin DE
影响因子：
64.8
作者：
Cernilogar, Filippo M.;Onorati, Maria Cristina;Kothe, Greg O.;Burroughs, A. Maxwell;Parsi, Krishna Mohan;Breiling, Achim;Lo Sardo, Federica;Saxena, Alka;Miyoshi, Keita;Siomi, Haruhiko;Siomi, Mikiko C.;Carninci, Piero;Gilmour, David S.;Corona, Davide F. V.;Orlando, Valerio
通讯作者：
Orlando, Valerio
影响因子：
5.3
作者：
Ballarino, Monica;Pagano, Francesca;Bozzoni, Irene
通讯作者：
Bozzoni, Irene
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
16
作者：
Lassot, Irina;Latreille, Daniel;Kiernan, Rosemary E.
通讯作者：
Kiernan, Rosemary E.