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PreprintCited by 3Chromosomal and Genetic VariationsRNA Interference and Gene DeliveryRNA Research and Splicing

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piRNA processing by a trimeric Schlafen-domain nuclease

Open access
Podvalnaya, Nadezda, Bronkhorst, Alfred W., Lichtenberger, Raffael, Hellmann, Svenja, Nischwitz, Emily, Falk, Torben, Karaulanov, Emil, Butter, Falk, Falk, Sebastian, Ketting, René F.·2023·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2023.01.19.524756

Preprint — published as 10.1038/s41586-023-06588-2 · Paper page

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Abstract

Transposable elements are genomic parasites that expand within and spread between genomes 1 . Piwi proteins control transposon activity, notably in the germline 2,3 . These proteins recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step in this crucial 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 proteins (SLFL proteins), executes 5’-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 4 , and that this interaction enhances piRNA production in vivo . The identification of PUCH completes the repertoire of C. elegans piRNA biogenesis factors and uncovers a novel type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (Slfn) genes have been associated with immunity responses 5 , exposing a thus far unknown molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.

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Metadata

Authors
Podvalnaya, N., Bronkhorst, A. W., Lichtenberger, R., Hellmann, S., Nischwitz, E., Falk, T., Karaulanov, E., Butter, F., Falk, S., & Ketting, R. F.
Affiliations
  • Institute of Molecular Biology (DE)
  • University of Vienna (AT)
  • Johannes Gutenberg University Mainz (DE)
Corresponding author
  • Falk, Sebastian
  • Ketting, René F.
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2023-01-20
DOI
10.1101/2023.01.19.524756
OpenAlex
W4317565990
Cited by
3
References
2
Citations by year
2024: 1 · 2023: 2
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (TRR319, 439669440, INST 247/870-1FUGG)
  • European Synchrotron Radiation Facility
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
piRNA biogenesis, m7G cap, transposable elements, Caenorhabditis elegans, PIWI proteins, RNA endonuclease

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