Human Alu RNA Is a Modular Transacting Repressor of mRNA Transcription during Heat Shock

Department of Chemistry and Biochemistry, University of Colorado at Boulder, 215 UCB, Boulder, CO 80309-0215, USA.
Molecular cell (Impact Factor: 14.02). 03/2008; 29(4):499-509. DOI: 10.1016/j.molcel.2007.12.013
Source: PubMed


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 B1 RNA, also bind Pol II 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.

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Available from: Celso Espinoza, Jul 22, 2015
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    • "For instance, the expression of an Alu in the promoter of the epsilon-globin gene was found to negatively regulate globin gene expression by transcriptional interference [112]. Recently, Alu RNA was found to be a modular transacting repressor of mRNA transcription [113]. Importantly, such transcriptional suppression was found to be specific and limited to certain genes. "
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    • "In mammals, the polymerase III (pol III) transcribed SINEs are up-regulated during heat shock and enter the complexes that target promoters of repressed genes (Ponicsan et al., 2010). Intriguingly, in humans and mouse two different and unrelated SINEs [the human Alu is derived from a 7SL RNA (Batzer and Deininger, 2002), the mouse B2 from a tRNA (Daniels and Deininger, 1985)] are part of this heat shock response (Allen et al., 2004; Mariner et al., 2008). Hence, different SINEs have been recruited for this task during mammalian evolution, suggesting that increased transcription during heat shock is a common feature of these SINEs. "
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