TY  - JOUR
AU  - Horos, Rastislav
AU  - Büscher, Magdalena
AU  - Kleinendorst, Rozemarijn
AU  - Alleaume, Anne-Marie
AU  - Tarafder, Abul K.
AU  - Schwarzl, Thomas
AU  - Dziuba, Dmytro
AU  - Tischer, Christian
AU  - Zielonka, Elisabeth M.
AU  - Adak, Asli
AU  - Castello, Alfredo
AU  - Huber, Wolfgang
AU  - Sachse, Carsten
AU  - Hentze, Matthias W.
TI  - The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy
JO  - Cell
VL  - 176
IS  - 5
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - FZJ-2019-02848
SP  - 1054 - 1067.e12
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30773316
UR  - <Go to ISI:>//WOS:000459257500010
DO  - DOI:10.1016/j.cell.2019.01.030
UR  - https://juser.fz-juelich.de/record/862554
ER  -