Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313: 320-324

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (Impact Factor: 33.61). 08/2006; 313(5785):320-4. DOI: 10.1126/science.1129333
Source: PubMed


In the Drosophila germline, repeat-associated small interfering RNAs (rasiRNAs) ensure genomic stability by silencing endogenous selfish genetic elements such as retrotransposons and repetitive sequences. Whereas small interfering RNAs (siRNAs) derive from both the sense and antisense strands of their double-stranded RNA precursors, rasiRNAs arise mainly from the antisense strand. rasiRNA production appears not to require Dicer-1, which makes microRNAs (miRNAs), or Dicer-2, which makes siRNAs, and rasiRNAs lack the 2',3' hydroxy termini characteristic of animal siRNA and miRNA. Unlike siRNAs and miRNAs, rasiRNAs function through the Piwi, rather than the Ago, Argonaute protein subfamily. Our data suggest that rasiRNAs protect the fly germline through a silencing mechanism distinct from both the miRNA and RNA interference pathways.

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    • "The 3 ′ cleavage fragments can be processed into secondary piRNAs, which in turn are able to cleave antisense piRNA precursors, thus closing a piRNA amplification loop termed ping-pong (Brennecke et al. 2007; Gunawardane et al. 2007). In mammals, most postnatal piRNAs are produced at the pachytene stage of meiosis from clusters depleted of repeat sequences that in mice are transcribed by A-MYB (Aravin et al. 2004, 2006; Girard et al. 2006; Grivna et al. 2006; Lau et al. 2006; Vagin et al. 2006; Li et al. 2013). "
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    ABSTRACT: Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions of most of the factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show that MOV10L1 exhibits 5'-to-3' directional RNA-unwinding activity in vitro and that a point mutation that abolishes this activity causes a failure in primary piRNA biogenesis in vivo. We demonstrate that MOV10L1 selectively binds piRNA precursor transcripts and is essential for the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Multiple analyses suggest an intimate coupling of piRNA precursor processing with elements of local secondary structures such as G quadruplexes. Our results support a model in which MOV10L1 RNA helicase activity promotes unwinding and funneling of the single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing. © 2015 Vourekas et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & Development 03/2015; 29(6). DOI:10.1101/gad.254631.114 · 10.80 Impact Factor
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    • "The first class is associated to Dicer endoribonuclease and has an important role in the control of TEs in plants (Matzke et al., 2009). piRNAs mediated the silencing through their interaction with piwi proteins (Vagin et al., 2006) and is the main mechanism of animal TE control. In D. melanogaster, piRNAs are generated from repeats and TE copies inserted in certain heterochromatic regions named piRNA clusters (Brennecke et al., 2007). "

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    • "The involvement of Piwi proteins and piRNAs in the degradation of target RNAs is supported by the observation that mutating cytoplasmic Piwi proteins usually results in upregulation of transposon RNAs. (Houwing et al., 2008; Reuter et al., 2011; Vagin et al., 2006; Watanabe et al., 2008). Although there is no convincing evidence indicating that piRNAs are involved in translational repression, some observations indicate that target mRNAs might be translationally repressed by Piwi proteins and piRNAs. "
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    ABSTRACT: Piwi proteins and Piwi-interacting RNAs (piRNAs) are essential for gametogenesis, embryogenesis, and stem cell maintenance in animals. Piwi proteins act on transposon RNAs by cleaving the RNAs and by interacting with factors involved in RNA regulation. Additionally, piRNAs generated from transposons and psuedogenes can be used by Piwi proteins to regulate mRNAs at the posttranscriptional level. Here we discuss piRNA biogenesis, recent findings on posttranscriptional regulation of mRNAs by the piRNA pathway, and the potential importance of this posttranscriptional regulation for a variety of biological processes such as gametogenesis, developmental transitions, and sex determination.
    Molecular Cell 10/2014; 56(1):18–27. DOI:10.1016/j.molcel.2014.09.012 · 14.02 Impact Factor
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