Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Protease-mediated processing of Argonaute proteins controls small RNA association

View ORCID ProfileRajani Kanth Gudipati, Kathrin Braun, View ORCID ProfileFoivos Gypas, View ORCID ProfileDaniel Hess, View ORCID ProfileJan Schreier, View ORCID ProfileSarah H. Carl, View ORCID ProfileRené F. Ketting, View ORCID ProfileHelge Großhans
doi: https://doi.org/10.1101/2020.12.09.417253
Rajani Kanth Gudipati
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rajani Kanth Gudipati
  • For correspondence: helge.grosshans@fmi.ch Rajani.gudipatti@fmi.ch
Kathrin Braun
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Foivos Gypas
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Foivos Gypas
Daniel Hess
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Daniel Hess
Jan Schreier
2Biology of Non-coding RNA, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jan Schreier
Sarah H. Carl
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sarah H. Carl
René F. Ketting
2Biology of Non-coding RNA, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for René F. Ketting
Helge Großhans
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland
3University of Basel, Petersplatz 1, 4056 Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Helge Großhans
  • For correspondence: helge.grosshans@fmi.ch Rajani.gudipatti@fmi.ch
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Small RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Desilencing of repeat- and transposon-derived transcripts, DNA damage and acute sterility ensue. These phenotypes are recapitulated when WAGO-1 and WAGO-3 are rendered resistant to DFP-3-mediated processing, identifying them as critical substrates of DPF-3. We conclude that N-terminal processing of Ago proteins regulates their activity and promotes discrimination of self from non-self by ensuring association with the proper complement of small RNAs.

Figure

Graphical Abstract: The role of DPF-3 in the fertility of the animalsIn wild type animals, the WAGO-1 and WAGO-3 Argonaute proteins are produced as immature pro-proteins with N-termini (N) that are unusually rich in prolines (P). N-terminal processing by DPF-3 is required for loading of the proper small RNA cargo and stabilization of WAGO-3. Accordingly, loss of this processing activity causes desilencing of transposable elements (TE), cell death and sterility.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Lead contact: HG

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted December 09, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Protease-mediated processing of Argonaute proteins controls small RNA association
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Protease-mediated processing of Argonaute proteins controls small RNA association
Rajani Kanth Gudipati, Kathrin Braun, Foivos Gypas, Daniel Hess, Jan Schreier, Sarah H. Carl, René F. Ketting, Helge Großhans
bioRxiv 2020.12.09.417253; doi: https://doi.org/10.1101/2020.12.09.417253
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Protease-mediated processing of Argonaute proteins controls small RNA association
Rajani Kanth Gudipati, Kathrin Braun, Foivos Gypas, Daniel Hess, Jan Schreier, Sarah H. Carl, René F. Ketting, Helge Großhans
bioRxiv 2020.12.09.417253; doi: https://doi.org/10.1101/2020.12.09.417253

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Molecular Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13248)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47368)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)