2. Academic Validation
  3. Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE

Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE

  • Nat Struct Mol Biol. 2025 Jan 7. doi: 10.1038/s41594-024-01446-9.
Simon Bressendorff # 1,  Ida Marie Zobbe Sjøgaard # 1,  Andreas Prestel 2,  Vasileios Voutsinos 3,  Martin D Jansson 4,  Patrice Ménard 4,  Anders H Lund 4,  Rasmus Hartmann-Petersen 3,  Birthe B Kragelund 2,  Christian Poulsen 1 5,  Peter Brodersen 6
Affiliations

Affiliations

  • 1 Copenhagen Plant Science Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • 2 Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • 3 Kaj Ulrik Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • 4 Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
  • 5 Novo Nordisk, Måløv, Denmark.
  • 6 Copenhagen Plant Science Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark. pbrodersen@bio.ku.dk.
  • # Contributed equally.
PMID: 39774835 DOI: 10.1038/s41594-024-01446-9
Abstract

ARGONAUTE (AGO) proteins bind to small non-coding RNAs to form RNA-induced silencing complexes. In the RNA-bound state, AGO is stable while RNA-free AGO turns over rapidly. Molecular features unique to RNA-free AGO that allow its specific recognition and degradation remain unknown. Here, we identify a confined, linear region in Arabidopsis AGO1 and human Ago2, the N-coil, as a structural switch with preferential accessibility in the RNA-free state. RNA-free Arabidopsis AGO1 interacts with the Autophagy cargo receptor ATI1 by direct contact with specific N-coil amino acid residues whose mutation reduces the degradation rate of RNA-free AGO1 in vivo. The N-coil of human Ago2 has similar degron activity dependent on residues in positions equivalent to those required for the Arabidopsis AGO1-ATI1 interaction. These results elucidate the molecular basis for specific recognition and degradation of the RNA-free state of eukaryotic AGO proteins.

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