Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc

Voigt, Franka; Reuter, M.; Kasaruho, Anisa; Schulz, Eike C.; Pillai, Ramesh S.; Barábas, O.

doi:10.1261/rna.034967.112

Cited by 63 publications

(48 citation statements)

References 31 publications

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“…PPIFs were identified biochemically by Piwi HITS-CLIP (Vourekas et al 2012) and genetically in the Tdrkh mutant mice (Saxe et al 2013). MOV10L1 and the endonuclease, which is most likely a mZuc dimer ( Haase et al 2010;Ipsaro et al 2012;Nishimasu et al 2012;Voigt et al 2012), are both required for the generation of PPIFs, indicating that these activities are functionally linked. We envision that MOV10L1 helicase activity is essential for proper piRNA precursor "feeding" to the endonuclease for cleavage.…”

Section: Discussionmentioning

confidence: 99%

“…There is substantial evidence from genetic and cell culture experiments that Zuc is essential for primary piRNA biogenesis (Pane et al 2007;Malone et al 2009;Haase et al 2010;Saito et al 2010;Watanabe et al 2011), and it was recently shown both structurally and biochemically that Zuc is an endonuclease that cleaves ssRNA and leaves a 5 ′ phosphate end (Ipsaro et al 2012;Nishimasu et al 2012;Voigt et al 2012). Therefore, Zuc fits the description for the endonuclease that generates the 5 ′ ends of piRNA intermediates, but direct proof of this is lacking.…”

Section: Discussionmentioning

confidence: 99%

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The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing

et al. 2015

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“…2A). In the first step, an endonuclease, possibly Zucchini, cleaves precursor transcripts to generate 59 phosphorylated intermediate RNAs that are then loaded into Piwi proteins (Ipsaro et al 2012;Nishimasu et al 2012;Voigt et al 2012). During the next step, another nuclease trims the intermediate from its 39 end until it reaches the footprint protected by the Piwi protein (Kawaoka et al 2011).…”

Section: Pirnas Provide Long-term Genetic Memory Of Transposon Invasionsmentioning

confidence: 99%

Small but sturdy: small RNAs in cellular memory and epigenetics

2014

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Cells in multicellular organisms have distinct identities characterized by their profiles of expressed genes. Cell identities can be stable over a long time and through multiple cellular divisions but are also responsive to extracellular signals. Since the DNA sequence is identical in all cells, a “cellular memory” of expression profiles is achieved by what are defined as epigenetic mechanisms. Two major molecular principles—networks of transcription factors and maintenance of cis-chromatin modifications—have been implicated in maintaining cellular memory. Here we describe recent studies demonstrating that short noncoding RNAs can also provide molecular signals that define epigenetic states of cells. Small RNAs can act independently or cooperate with chromatin modifications to achieve long-lasting effects necessary for cellular memory and transgenerational inheritance.

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“…Recent studies have implicated Zucchini, an HKD (Hys-Lys-Asp) family nuclease, in the production of the 59 ends of primary piRNAs (Haase et al 2010;Olivieri et al 2010;Ipsaro et al 2012;Nishimasu et al 2012;Voigt et al 2012). Biochemical studies in Bombyx cell extracts have provided support for a model in which the 39 ends of piRNAs are formed by exonucleolytic resection of longer RNAs following their loading into Piwi family proteins, although the enzymes responsible for this reaction are unknown (Kawaoka et al 2011).…”

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confidence: 99%

Multiple roles for Piwi in silencing Drosophila transposons

Hammell²,

2013

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Silencing of transposons in the Drosophila ovary relies on three Piwi family proteins-Piwi, Aubergine (Aub), and Ago3-acting in concert with their small RNA guides, the Piwi-interacting RNAs (piRNAs). Aub and Ago3 are found in the germ cell cytoplasm, where they function in the ping-pong cycle to consume transposon mRNAs. The nuclear Piwi protein is required for transposon silencing in both germ and somatic follicle cells, yet the precise mechanisms by which Piwi acts remain largely unclear. We investigated the role of Piwi by combining cell typespecific knockdowns with measurements of steady-state transposon mRNA levels, nascent RNA synthesis, chromatin state, and small RNA abundance. In somatic cells, Piwi loss led to concerted effects on nascent transcripts and transposon mRNAs, indicating that Piwi acts through transcriptional gene silencing (TGS). In germ cells, Piwi loss showed disproportionate impacts on steady-state RNA levels, indicating that it also exerts an effect on post-transcriptional gene silencing (PTGS). Piwi knockdown affected levels of germ cell piRNAs presumably bound to Aub and Ago3, perhaps explaining its post-transcriptional impacts. Overall, our results indicate that Piwi plays multiple roles in the piRNA pathway, in part enforcing transposon repression through effects on local chromatin states and transcription but also participating in germ cell piRNA biogenesis.

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Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc

Cited by 63 publications

References 31 publications

The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing

The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing

Small but sturdy: small RNAs in cellular memory and epigenetics

Multiple roles for Piwi in silencing Drosophila transposons

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