Genomic gems: SINE RNAs regulate mRNA production.
ABSTRACT Mammalian short interspersed elements (SINEs) are abundant retrotransposons that have long been considered junk DNA; however, RNAs transcribed from mouse B2 and human Alu SINEs have recently been found to control mRNA production at multiple levels. Upon cell stress B2 and Alu RNAs bind RNA polymerase II (Pol II) and repress transcription of some protein-encoding genes. Bi-directional transcription of a B2 SINE establishes a boundary that places the growth hormone locus in a permissive chromatin state during mouse development. Alu RNAs embedded in Pol II transcripts can promote evolution and proteome diversity through exonization via alternative splicing. Given the diverse means by which SINE encoded RNAs impact production of mRNAs, this genomic junk is proving to contain hidden gems.
Article: Acute stress and hippocampal histone H3 lysine 9 trimethylation, a retrotransposon silencing response.[show abstract] [hide abstract]
ABSTRACT: The hippocampus is a highly plastic brain region particularly susceptible to the effects of environmental stress; it also shows dynamic changes in epigenetic marks in response to stress and learning. We have previously shown that, in the rat, acute (30 min) restraint stress induces a substantial, regionally specific, increase in hippocampal levels of the repressive histone H3 lysine 9 trimethylation (H3K9me3). Because of the large magnitude of this effect and the fact that stress can induce the expression of endogenous retroviruses and transposable elements in many systems, we hypothesized that the H3K9me3 response was targeted to these elements as a means of containing potential genomic instability. We used ChIP coupled with next generation sequencing (ChIP-Seq) to determine the genomic localization of the H3K9me3 response. Although there was a general increase in this response across the genome, our results validated this hypothesis by demonstrating that stress increases H3K9me3 enrichment at transposable element loci and, using RT-PCR, we demonstrate that this effect represses expression of intracisternal-A particle endogenous retrovirus elements and B2 short interspersed elements, but it does not appear to have a repressive effect on long interspersed element RNA. In addition, we present data showing that the histone H3K9-specific methyltransferases Suv39h2 is up-regulated by acute stress in the hippocampus, and that this may explain the hippocampal specificity we observe. These results are a unique demonstration of the regulatory effect of environmental stress, via an epigenetic mark, on the vast genomic terra incognita represented by transposable elements.Proceedings of the National Academy of Sciences 10/2012; 109(43):17657-62. · 9.68 Impact Factor
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ABSTRACT: Following the initial discovery of the heat shock RNA omega (hsrω) gene of Drosophila melanogaster to be non-coding (nc) and also inducible by cell stress, other stress-inducible long non-coding RNAs (lncRNA) have been described in diverse organisms. In view of the rapid sequence divergence of lncRNAs, present knowledge of stress trasncriptome is limited and fragmented. Several known stress-related lncRNAs, associated with specific nuclear speckled domains or nucleolus, provide structural base for sequestering diverse RNA-processing/regulatory proteins. Others have roles in transcriptional or translational inhibition during stress or in signaling pathways; functions of several other lncRNAs are not yet known. Most stress-related lncRNAs act primarily by modulating activity of the proteins to which they bind or by sequestering specific sets of proteins away from the active pool. A common emerging theme is that a given lncRNA targets one or more protein/s with key role/s in the cascade of events triggered by the stress and therefore has a widespread integrative effect. Since proteins associate with RNA through short sequence motifs, the overall base sequence of functionally similar ncRNAs is often not conserved except for specific motifs. The rapid evolvability of ncRNA sequences provides elegant modules for adaptability to changing environment as binding of one or the other protein to ncRNA can alter its structure and functions in distinct ways. Thus the stress-related lncRNAs act as hubs in the cellular networks to coordinate activities of the members within and between different networks to maintain cellular homeostasis for survival or to trigger cell death. WIREs RNA 2012. doi: 10.1002/wrna.1135 For further resources related to this article, please visit the WIREs website. The author declares no conflict of interest.WIREs RNA 09/2012; 3(6):779-96.
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ABSTRACT: During cellular stress response, a widespread inhibition of transcription and blockade of splicing and other post-transcriptional processing is detected, while certain specific genes are induced. In particular, free-living cells constantly monitor temperature. When the thermal condition changes, they activate a set of genes coding for proteins that participate in the response. Non-coding RNAs, ncRNAs, and conformational changes in specific regions of mRNAs seem also to be crucial regulators that enable the cell to adjust its physiology to environmental changes. They exert their effects following the same principles in all organisms and may affect all steps of gene expression. These ncRNAs and structural elements as related to thermal stress response in bacteria are reviewed. The resemblances to eukaryotic ncRNAs are highlighted.FEBS letters 10/2012; · 3.54 Impact Factor