A Genome-wide RNAi Screen Draws a Genetic Framework for Transposon Control and Primary piRNA Biogenesis in Drosophila

Muerdter, Felix; Guzzardo, Paloma M.; Gillis, Jesse; Luo, Yicheng; Yu, Yang; Chen, Caifu; Fekete, Richard A.; Hannon, Gregory J.

doi:10.1016/j.molcel.2013.04.006

Cited by 165 publications

(219 citation statements)

References 59 publications

Supporting

Mentioning

205

Contrasting

Order By: Relevance

“…Several large-scale RNAi screens using qPCR-based analysis of transposon expression or LacZ reporters for either somatic or germ cell piRNA pathway components have also identified factors involved in piRNA biogenesis (Czech et al, 2013;Handler et al, 2013;Muerdter et al, 2013). One such factor is the uncharacterised protein CG2183 (Gasz), which localises with Zuc to mitochondria and likely acts as an adapter that recruits a complex of Armitage (a non-DEAD-box helicase) and Piwi to mitochondria for piRNA loading and maturation (Czech et al, 2013;Handler et al, 2013).…”

Section: The Birth Of Pirnasmentioning

confidence: 99%

“…2A). piRISC-induced TGS also requires the zinc-finger protein GTSF-1/Asterix, which likely directly interacts with Piwi and is required for establishment of H3K9 methylation (Donertas et al, 2013;Handler et al, 2013;Muerdter et al, 2013). Furthermore, histone methylation may not be the final silencing mark; the high mobility group protein Maelstrom, like Piwi, is required for POL II inhibition; however, changes in H3K9me3 methylation following mael knockdown are modest compared with the effects seen upon piwi knockdown, indicating that Mael acts downstream of Piwi and histone methylation (Sienski et al, 2012).…”

Section: Mechanisms Of Pirna-mediated Transcriptional Silencingmentioning

confidence: 99%

See 1 more Smart Citation

piRNAs: from biogenesis to function

2014

View full text Add to dashboard Cite

Distinguishing self from non-self plays a crucial role in safeguarding the germlines of metazoa from mobile DNA elements. Since their discovery less than a decade ago, Piwi-interacting RNAs ( piRNAs) have been shown to repress transposable elements in the germline and, hence, have been at the forefront of research aimed at understanding the mechanisms that maintain germline integrity. More recently, roles for piRNAs in gene regulation have emerged. In this Review, we highlight recent advances made in understanding piRNA function, highlighting the divergent nature of piRNA biogenesis in different organisms, and discussing the mechanisms of piRNA action during transcriptional regulation and in transgenerational epigenetic inheritance.

show abstract

Section: The Birth Of Pirnasmentioning

confidence: 99%

Section: Mechanisms Of Pirna-mediated Transcriptional Silencingmentioning

confidence: 99%

piRNAs: from biogenesis to function

2014

View full text Add to dashboard Cite

show abstract

“…Although miRNAs and endo-siRNAs are expressed in both animals and plants, piRNA expression is largely restricted to animal gonads, where they primarily mediate TE silencing for genome integrity and germ cell development (Thomson and Lin 2009;Siomi et al 2011). piRNAs act as guides for the cleavage of TE transcripts by PIWI protein Slicer activity in the cytoplasm, which often couples with the ping-pong cycle, or for Slicer-independent heterochromatin formation at TE loci in the nucleus (Sienski et al 2012;Dönertas et al 2013;Huang et al 2013;Le Thomas et al 2013;Muerdter et al 2013;Ohtani et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

Hirano

Iwasaki

Lin

et al. 2014

RNA

View full text Add to dashboard Cite

Small RNAs mediate gene silencing by binding Argonaute/Piwi proteins to regulate target RNAs. Here, we describe small RNA profiling of the adult testes of Callithrix jacchus, the common marmoset. The most abundant class of small RNAs in the adult testis was piRNAs, although 353 novel miRNAs but few endo-siRNAs were also identified. MARWI, a marmoset homolog of mouse MIWI and a very abundant PIWI in adult testes, associates with piRNAs that show characteristics of mouse pachytene piRNAs. As in other mammals, most marmoset piRNAs are derived from conserved clustered regions in the genome, which are annotated as intergenic regions. However, unlike in mice, marmoset piRNA clusters are also found on the X chromosome, suggesting escape from meiotic sex chromosome inactivation by the X-linked clusters. Some of the piRNA clusters identified contain antisenseorientated pseudogenes, suggesting the possibility that pseudogene-derived piRNAs may regulate parental functional proteincoding genes. More piRNAs map to transposable element (TE) subfamilies when they have copies in piRNA clusters. In addition, the strand bias observed for piRNAs mapped to each TE subfamily correlates with the polarity of copies inserted in clusters. These findings suggest that pachytene piRNA clusters determine the abundance and strand-bias of TE-derived piRNAs, may regulate protein-coding genes via pseudogene-derived piRNAs, and may even play roles in meiosis in the adult marmoset testis.

show abstract

“…Alternatively, if Piwi is translocated to the nucleus, factors including Maelstrom and chromatin modifiers are recruited to genomic loci to establish hetrochromatic silencing marks (Box 2). Other effector proteins, including asterix/Gtsf1 show a pronounced effect on transposon silencing while leaving piRNA levels unchanged [51,117,118]. The precise mechanisms by which these factors are recruited and enforce TGS are being investigated.…”

Section: Piwismentioning

confidence: 99%

“…1d). After cleavage, the parsed products retain 5′ phosphate and 3′ hydroxyl chemistry, and can presumably be loaded into Piwi.Recent genome-wide screens by multiple groups identified a large number of piRNA pathway components [49][50][51], and it is presumed that the current model of piRNA silencing is rather incomplete. Nonetheless, two proteins in Drosophila, Rhino and Cutoff, were shown to be necessary for the production of dual-strand piRNA cluster transcripts [52,53].…”

mentioning

confidence: 99%

From guide to target: molecular insights into eukaryotic RNA-interference machinery

Ipsaro

Joshua‐Tor

2015

Nat Struct Mol Biol

216

144

View full text Add to dashboard Cite

Since its relatively recent discovery, RNA interference (RNAi) has emerged as a potent, specific, and ubiquitous means of gene regulation. Through a number of pathways that are conserved from yeast to humans, small non-coding RNAs direct molecular machinery to silence gene expression. In this review, we focus on mechanisms and structures that govern RNA silencing in higher organisms. In addition to highlighting recent advances, parallels and differences between RNAi pathways are discussed. Together, the studies reviewed herein reveal the versatility and programmability of RNA-induced Silencing Complexes (RISCs) and emphasize the importance of both upstream biogenesis and downstream silencing factors. Discovery and Biological Perspectives of RNA interferenceRNAi was first described by Fire and Mello in the 1990s when, in an attempt to use antisense RNA to down-regulate gene expression, they observed that double-stranded RNA (dsRNA) was more potent than sense or anti-sense RNA alone [1]. This seminal work boasted robust and specific gene knock down in addition to coining the term "RNA interference" (RNAi). Shortly beforehand, the discovery of individual regulatory RNAs in C. elegans hinted that small, non-coding RNAs might be a pervasive means of gene regulation in higher organisms [2,3]. In the following decade, with the mechanistic insight of Fire and Mello's work in hand, this idea was confirmed and it is now accepted that wellover 1,000 small RNAs are encoded in the human genome that may regulate over 60% of our genes [4,5]. It also became apparent that several seemingly disconnected phenomena are variations of RNAi-type pathways including co-suppression in plants, DNA elimination in Tetrahymena, and quelling in Neurospora [6]. The prevalence of RNAi is impressive and its importance is underscored by the fact that RNAi dysfunction is associated with numerous diseases and disorders including neurological maladies, cancers, and infertility.Shortly after the initial description of RNAi phenomenology, a burst of genetic, biochemical, biophysical, and bioinformatic efforts laid a strong foundation for identifying the molecular pathways, players, and parameters that govern silencing via RNAi. Work from Reprints and permissions information is available online at http://www.nature.com/reprints/index.html. HHMI Author ManuscriptHHMI Author Manuscript HHMI Author Manuscript numerous groups defined the molecular apparatus of RNAi as RISC (RNA-induced Silencing Complex), a ribonucleoprotein complex minimally comprised of a small singlestranded RNA (~20-31 nucleotides) and an Argonaute protein which serves as the effector molecule (reviewed in [7]). In this configuration, the loaded "guide" RNA acts as a specificity determinant that directs Argonaute and any other associated machinery to the target. The guide-loaded Argonaute platform underlies every example in the expansive array of known RNAi pathways in eukaryotes regardless of the source of the guide (structured loci, transposons, viral, etc.), the machinery ...

show abstract

A Genome-wide RNAi Screen Draws a Genetic Framework for Transposon Control and Primary piRNA Biogenesis in Drosophila

Cited by 165 publications

References 59 publications

piRNAs: from biogenesis to function

piRNAs: from biogenesis to function

Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

From guide to target: molecular insights into eukaryotic RNA-interference machinery

Contact Info

Product

Resources

About