The small non-coding vault RNA1-1 acts as a riboregulator of autophagy

Horos, R. et al. (2019) The small non-coding vault RNA1-1 acts as a riboregulator of autophagy. Cell, 176(5), 1054-1067.e12. (doi: 10.1016/j.cell.2019.01.030) (PMID:30773316)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Castello, Professor Alfredo
Authors: Horos, R., Büscher, M., Kleinendorst, R., Alleaume, A.-M., Tarafder, A. K., Schwarzl, T., Dziuba, D., Tischer, C., Zielonka, E. M., Adak, A., Castello, A., Huber, W., Sachse, C., and Hentze, M. W.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN:0092-8674
ISSN (Online):1097-4172
Published Online:14 February 2019
Copyright Holders:Copyright © 2019 Elsevier Inc.
First Published:First published in Cell 176(5): 1054-1067.e12
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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