Vault RNA emerges as a regulator of selective autophagy

Autophagy. 2019 Aug;15(8):1463-1464. doi: 10.1080/15548627.2019.1609861. Epub 2019 May 3.

Abstract

The selective autophagic receptor SQSTM1/p62 ushers cargo to phagophores, the precursors of autophagosomes, and serves as a platform for autophagy initiation. We discovered that SQSTM1 is an RNA-binding protein that interacts with vault RNAs. Vault RNAs are small non-coding RNAs found in many eukaryotes and transcribed by POLR3 (RNA polymerase III). The levels of VTRNA1-1 (vault RNA 1-1) regulate SQSTM1-mediated autophagy and ubiquitin aggregate clearance. Vault RNA interferes with oligomerization of SQSTM1, which is in turn critical for its autophagic function. Our study uncovered a novel mode of regulation of a protein's activity by RNA, termed riboregulation.

Keywords: SQSTM1; VTRNA1-1; non-coding RNA; p62; selective autophagy; vault RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Humans
  • RNA / metabolism*
  • Sequestosome-1 Protein / chemistry
  • Sequestosome-1 Protein / metabolism

Substances

  • Sequestosome-1 Protein
  • RNA

Grants and funding

This work was supported by a European Research Council Advanced Grant and by a grant from the Virtual Liver Consortium (German Ministry for Education and Research) awarded to Matthias W. Hentze.