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. 2014 Mar 6:4:e28439.
doi: 10.4161/mge.28439. eCollection 2014.

Control of mammalian retrotransposons by cellular RNA processing activities

Sara R Heras  1 , Sara Macias  2 , Javier F Cáceres  2 , Jose L Garcia-Perez  1
Affiliations

Control of mammalian retrotransposons by cellular RNA processing activities

Sara R Heras et al. Mob Genet Elements. .

Abstract

Retrotransposons make up roughly 50% of the mammalian genome and have played an important role in genome evolution. A small fraction of non-LTR retrotransposons, LINE-1 and SINE elements, is currently active in the human genome. These elements move in our genome using an intermediate RNA and a reverse transcriptase activity by a copy and paste mechanism. Their ongoing mobilization can impact the human genome leading to several human disorders. However, how the cell controls the activity of these elements minimizing their mutagenic effect is not fully understood. Recent studies have highlighted that the intermediate RNA of retrotransposons is a target of different mechanisms that limit the mobilization of endogenous retrotransposons in mammals. Here, we provide an overview of recent discoveries that show how RNA processing events can act to control the activity of mammalian retrotransposons and discuss several arising questions that remain to be answered.

Keywords: DGCR8; Dicer; Drosha; LINE-1; Microprocessor; SINE-1; microRNAs; retrotransposon; small RNAs; transposable elements.

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Figures

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Figure 1. Regulation of mammalian retrotransposons at the RNA level. (A) DNA-Methylation of L1 promoters (5′UTR) inhibits its expression. (B) The Microprocessor process structured regions in Alu and L1 derived transcripts, reducing their levels. (C) L1-RNAs can be degraded by the exosome-associated 3′→5′ exoribonuclease Rrp6 and the 5′→3′ exoribonuclease Xrn2; these may occur also after being cleaved by Microprocessor. (D) Double-strand RNAs produced by transcription from both sense and antisense promoters may inhibit L1 retrotransposition by an RNAi mechanism (E). (E) siRNAs are generated from dsRNA in the cytoplasm by Dicer processing and loaded onto AGO proteins targeting L1 RNAs. (F) The processing of L1 and Alu RNAs by the Microprocessor could generate a pre-microRNA-like structure that could be further processed by Dicer in the cytoplasm, generating mature miRNAs loaded in AGO proteins. (G) piRNAs are processed from RNA precursors that are transcribed from particular intergenic repetitive elements known as piRNA clusters. (H) Primary piRNAs are amplified through the ping-pong pathway. Thus, two different piwi proteins, MILI and MIWI2, are associated with sense (brown line) and antisense piRNAs (green line), respectively. piRNAs then may act as guides to cleave complementary transposon transcripts, which requires the endonuclease activity of piwi proteins. (I) Some piwi-like proteins are also localized in the nucleus, where they might participate in DNA-methylation TE sequences (A).
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Comment on

  • Heras SR, Macias S, Plass M, Fernandez N, Cano D, Eyras E, Garcia-Perez JL, Cáceres JF. The Microprocessor controls the activity of mammalian retrotransposons. Nat Struct Mol Biol. 2013;20:1173–81. doi: 10.1038/nsmb.2658.

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