Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock

Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock
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DOI:
10.1016/j.molcel.2007.12.013
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发表时间:
2008-02-29
期刊:
影响因子:
16
通讯作者:
Goodrich, James A.
Goodrich, James A.
中科院分区:
生物学1区
文献类型:
--
作者:
Mariner, Peter D.;Walters, Ryan D.;Goodrich, James A.

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非编码RNA(ncRNA)最近被发现以反式调节mRNA转录,这是传统上保留给蛋白质的作用。ncRNA作为transacting转录调节因子的广泛性和它们响应的信号的多样性现在才被认识到。在这里,我们表明,人类铝RNA,转录短散布元件(西内斯),是一个反式转录抑制剂在细胞热休克反应。Alu RNA通过结合RNA聚合酶II(Pol II)并在体外和人类细胞中进入启动子处的复合物来阻断转录。Alu RNA的转录抑制涉及两个松散结构的模块化结构域,这一特性让人想起经典的蛋白质转录调节因子。另外两种SINE RNA,人scAlu RNA和小鼠131 RNA,也结合Pol 11,但在体外不抑制转录。这些研究解释了为什么小鼠细胞含有两种主要的西内斯,而人类细胞只含有一种。
Noncoding RNAs (ncRNAs) have recently been discovered to regulate mRNA transcription in trans, a role traditionally reserved for proteins. The breadth of ncRNAs as transacting transcriptional regulators and the diversity of signals to which they respond are only now becoming recognized. Here we show that human Alu RNA, transcribed from short interspersed elements (SINEs), is a transacting transcriptional repressor during the cellular heat shock response. Alu RNA blocks transcription by binding RNA polymerase II (Pol II) and entering complexes at promoters in vitro and in human cells. Transcriptional repression by Alu RNA involves two loosely structured domains that are modular, a property reminiscent of classical protein transcriptional regulators. Two other SINE RNAs, human scAlu RNA and mouse 131 RNA, also bind Pol 11 but do not repress transcription in vitro. These studies provide an explanation for why mouse cells harbor two major classes of SINEs, whereas human cells contain only one.