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 example, they can affect transcription locally on the gene level (Martens et al., 2004; Martianov et al., 2007; Osato et al., 2007; Hirota et al., 2008) as well as target transcription regulators and thus affect transcription of many genes (Feng et al., 2006; Goodrich and Kugel, 2006). They can also target RNA polymerase II in human and mouse (Espinoza et al., 2007; Mariner et al., 2008) and thus affect the expression of an even broader range of genes. Furthermore, lincRNAs participate in the regulation of splicing (Munroe and Lazar, 1991; Beltran et al., 2008) and translation (Wang et al., 2005; Centonze et al., 2007). "
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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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    • "Apart from being detrimental or neutral, a minority of events has the potential to turn out beneficial. TEs of a certain class might harbor not only TFBS, but also numerous other functional sequences in their consensus sequences, and, perhaps , mainly because these elements are defined by their designation, proposals with highly diverse functions are being published, even involving TEs with very narrow phylogenetic distributions (Allen et al. 2004; Espinoza et al. 2004, 2007; Lunyak et al. 2007; Mariner et al. 2008; Gong and Maquat 2011; Yakovchuk et al. 2011; Carrieri et al. 2012; Jady et al. 2012; Holdt et al. 2013; Ponicsan et al. 2013; Wang et al. 2013). "
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