2. Academic Validation
  3. The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy

The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy

  • Cell. 2019 Feb 21;176(5):1054-1067.e12. doi: 10.1016/j.cell.2019.01.030.
Rastislav Horos 1,  Magdalena Büscher 2,  Rozemarijn Kleinendorst 2,  Anne-Marie Alleaume 2,  Abul K Tarafder 2,  Thomas Schwarzl 2,  Dmytro Dziuba 2,  Christian Tischer 2,  Elisabeth M Zielonka 2,  Asli Adak 2,  Alfredo Castello 3,  Wolfgang Huber 2,  Carsten Sachse 4,  Matthias W Hentze 5
Affiliations

Affiliations

  • 1 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: [email protected].
  • 2 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
  • 3 Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • 4 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons/ER-C3 Structural Biology, Wilhem-Johnen-Straße, 52425 Jülich, Germany.
  • 5 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: [email protected].
PMID: 30773316 DOI: 10.1016/j.cell.2019.01.030
Abstract

Vault RNAs (vtRNA) are small non-coding RNAs transcribed by RNA polymerase III found in many eukaryotes. Although they have been linked to drug resistance, Apoptosis, and viral replication, their molecular functions remain unclear. Here, we show that vault RNAs directly bind the Autophagy receptor sequestosome-1/p62 in human and murine cells. Overexpression of human vtRNA1-1 inhibits, while its antisense LNA-mediated knockdown enhances p62-dependent Autophagy. Starvation of cells reduces the steady-state and p62-bound levels of vault RNA1-1 and induces Autophagy. Mechanistically, p62 mutants that fail to bind vtRNAs display increased p62 homo-oligomerization and augmented interaction with autophagic effectors. Thus, vtRNA1-1 directly regulates selective Autophagy by binding p62 and interference with oligomerization, a critical step of p62 function. Our data uncover a striking example of the potential of RNA to control protein functions directly, as previously recognized for protein-protein interactions and post-translational modifications.

Keywords

SQSTM1; autophagy; non-coding RNA; p62; sequestosome-1; starvation; vault RNA; vtRNA; vtRNA1-1.

Figures
Products