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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    ABSTRACT: DNA methylation primarily occurs on CpG dinucleotides and plays an important role in transcriptional regulations during tissue development and cell differentiation. Over 25% of CpG dinucleotides in the human genome reside within Alu elements, the most abundant human repeats. The methylation of Alu elements is an important mechanism to suppress Alu transcription and subsequent retrotransposition. Decades of studies revealed that Alu methylation is highly dynamic during early development and aging. Recently, many environmental factors were shown to have a great impact on Alu methylation. In addition, aberrant Alu methylation has been documented to be an early event in many tumors and Alu methylation levels have been associated with tumor aggressiveness. The assessment of the Alu methylation has become an important approach for early diagnosis and/or prognosis of cancer. This review focuses on the dynamic Alu methylation during development, aging, and tumor genesis. The cause and consequence of Alu methylation changes will be discussed.
    BioMed Research International 08/2014; 2014:784706. DOI:10.1155/2014/784706 · 2.71 Impact Factor
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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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    Cold Spring Harbor perspectives in biology 07/2014; 6(12). DOI:10.1101/cshperspect.a016089 · 8.68 Impact Factor
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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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    ABSTRACT: Transposable elements (TEs) are ubiquitous in eukaryotic genomes. Barbara McClintock's famous notion of TEs acting as controlling elements modifying the genetic response of an organism upon exposure to stressful environments has since been solidly supported in a series of model organisms. This requires the TE activity response to possess an element of specificity and be targeted toward certain parts of the genome. We propose that a similar TE response is present in human cells, and that this stress response may drive the onset of human cancers. As such, TE-driven cancers may be viewed as an evolutionary by-product of organisms' abilities to genetically adapt to environmental stress.
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