Dataset Information

PiRNA processing by a trimeric Schlafen-domain-containing nuclease

ABSTRACT: Transposable elements are genomic parasites that expand within and spread between genomes. Piwi proteins control transposon activity, notably in the germline. These proteins recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step in this important genome immunity system. While the processing of piRNA precursors is an essential step in this process, many molecular details of this process remain unknown. We identify a novel endoribonuclease, PUCH, that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain (SLFNL) proteins, executes 5ï‚¢-end piRNA precursor cleavage. PUCH-mediated processing strictly requires an m7G-Cap and a Uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds piRNA precursors, and that this interaction enhances piRNA production in vivo. The identification of PUCH completes the C. elegans piRNA biogenesis repertoire and uncovers a novel type of RNA endonuclease formed by three SLFL proteins. Mammalian Slfn genes have been associated with immunity responses, exposing a novel molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: F Butter

LAB HEAD: Falk Butter

PROVIDER: PXD039502 | Pride | 2023-10-24

REPOSITORIES: Pride

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piRNA processing by a trimeric Schlafen-domain nuclease.

Podvalnaya Nadezda N Bronkhorst Alfred W AW Lichtenberger Raffael R Hellmann Svenja S Nischwitz Emily E Falk Torben T Karaulanov Emil E Butter Falk F Falk Sebastian S Ketting René F RF

Nature 20230927 7982

Transposable elements are genomic parasites that expand within and spread between genomes<sup>1</sup>. PIWI proteins control transposon activity, notably in the germline<sup>2,3</sup>. These proteins recognize their targets through small RNA co-factors named PIWI-interacting RNAs (piRNAs), making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. Although the processing of piRNA precursors is an essential step in this process, many of the molecular detail ...[more]

PMID: 37758951

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Project description:Small non-coding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of Metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that trans-generationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the H3K9me3 mark on genomic piRNA cluster sequences. The HP1 homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that trans-generationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels, by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. sequencing of argonaute-bound and total small RNAs from ovaries of different fly crosses: maternal deposition (MD) crosses, in which piRNAs from the P1152 locus are transmitted into the next generation through the mother. No maternak deposition (NMD) crosses, which are reciprocal to the MD crosses. Subsequently, no piRNAs from the P1152 locus are transmitted into the next generation. The strain P-1152, that carries insertion of P{lArB} construct in telomeric sequences of X chromosome (site 1A) is described in (Roche and Rio 1998). The strain BC69 that has insertion of P{A92} construct at a euchromatic location on chromosome 2L (site 35B10-35C1) is described in (Lemaitre et al. 1993).Both stocks were a generous gift from S. Ronsseray.

Dataset Information

PiRNA processing by a trimeric Schlafen-domain-containing nuclease

Publications

piRNA processing by a trimeric Schlafen-domain nuclease.

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