Biogenesis and germline functions of piRNA

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Development (Impact Factor: 6.46). 02/2008; 135(1):3-9. DOI: 10.1242/dev.006486
Source: PubMed


Small interfering RNAs and microRNAs are generated from double-stranded RNA precursors by the Dicer endonucleases, and function with Argonaute-family proteins to target transcript destruction or to silence translation. A distinct class of 24- to 30-nucleotide-long RNAs, produced by a Dicer-independent mechanism, associates with Piwi-class Argonaute proteins. Studies in flies, fish and mice implicate these Piwi-associated RNAs (piRNAs) in germline development, silencing of selfish DNA elements, and in maintaining germline DNA integrity. However, whether piRNAs primarily control chromatin organization, gene transcription, RNA stability or RNA translation is not well understood, neither is piRNA biogenesis. Here, we review recent studies of piRNA production and function, and discuss unanswered questions about this intriguing new class of small RNAs.

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    • "These functions prevent transposon propagation and earned PIWIs their nickname— " guardians of the genome " (Senti and Brennecke 2010). Altogether, piRNAs and PIWIs are indispensable for germline formation and maintenance, and mutations in piRNA pathway components usually cause sterility (Klattenhoff et al. 2007; Soper et al. 2008; Thomson and Lin 2009). Although most studies of piRNAs and PIWIs have been focused on transposon silencing in the germline, a number of studies have posited roles for piRNAs in somatic cells. "
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    ABSTRACT: PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations. © 2015 Zhou et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
    RNA 08/2015; 21(11). DOI:10.1261/rna.052456.115 · 4.94 Impact Factor
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    • "The third main class of small RNAs, piRNAs, are w24–31 nt long, derived from single-stranded piRNA precursor transcripts and processed in a Dicer-independent way (Vagin et al. 2006, Li et al. 2013). piRNAs associate with the PIWI subfamily of AGO proteins and are predominantly expressed in germ cells, where they are involved in transposon silencing through heterochromatin formation and RNA destabilization (Klattenhoff & Theurkauf 2008, Weick & Miska 2014). They play a major role in male development and fertility and will therefore be discussed in more detail below. "
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    ABSTRACT: A complex network of gene regulation and interaction drives male sex determination and differentiation. While many important protein-coding genes have been identified that are necessary for proper male development, many disorders of sex development in human are still unexplained at the molecular level. This suggests that key factors and regulatory mechanisms are still unknown. In recent years, extensive data have shown that different classes of non-coding RNA play a role in almost all developmental and physiological pathways. Here we review what is known about their role in male sex determination and differentiation not only in human and other mammals, but also other species. While for some processes a key role for non-coding RNA has been identified, we are still far from having a complete picture.
    Reproduction 05/2015; 150(3). DOI:10.1530/REP-15-0106 · 3.17 Impact Factor
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    • "Piwi-antisense piRNA complexes enter the nucleus, thus silencing gene expression and producing sense-strand piRNAs and antisense strand piRNA precursors that exported from the nucleus to nuage. The mature antisense piRNA–Ago3 complexes are then proposed to bind to and cleave sense-strand RNAs (Brennecke et al. 2007, Klattenhoff & Theurkauf 2008). A model for ping–pong cycle is shown in Fig. 2 "
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    ABSTRACT: Piwi-interacting RNAs (piRNAs) are a broad group of non-coding small RNAs with important biological functions in germline cells. It is well known that piRNAs can maintain genome integrity via silencing retrotransposons. Previous studies on the animal models harboring gene deletions have shown that the genes involved in piRNA biogenesis and their defective expression can result in the spermatogenic dysfunction. In the past decade, significant progress has been achieved for piRNAs and their roles in male germ cells. This review addresses the advances on piRNAs and piRNA biogenesis-associated genes, with a particular focus on the Moloney leukemia virus 10-like 1 (MOV10L1) gene, whose role in primary piRNA processing and in the 'ping-pong' cycle during secondary piRNA processing has been illustrated. The biological characteristics of piRNA has been summarized, and emphasis was laid on the roles of MOV10L1 in the mediation of piRNA biogenesis and retrotransposons silencing by DNA methylation. Furthermore, the association between MOV10L1 gene polymorphisms and complete maturation arrest in men has been discussed. Hence, thorough literature review was conducted in order to obtain a greater understanding of the function of MOV10L1 and its mechanisms underlying spermatogenesis in mice and humans.
    Reproduction (Cambridge, England) 02/2015; 149(5). DOI:10.1530/REP-14-0569 · 3.17 Impact Factor
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