학술논문
Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis.
Document Type
Academic Journal
Author
Ishtayeh H; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Galves M; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Barnatan TT; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Berdichevsky Y; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Amer-Sarsour F; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Pasmanik-Chor M; Bioinformatics Unit, G.S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel.; Braverman I; Department of Otolaryngology, Head and Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel.; Rappaport Faculty of Medicine, Technion, Haifa, Israel.; Blumen SC; Rappaport Faculty of Medicine, Technion, Haifa, Israel.; Department of Neurology, Hillel Yaffe Medical Center, Hadera, Israel.; Ashkenazi A; The Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Autophagy is an intracellular degradative process with an important role in cellular homeostasis. Here, we show that the RNA binding protein (RBP), heterogeneous nuclear ribonucleoprotein Q (HNRNPQ)/SYNCRIP is required to stimulate early events in autophagosome biogenesis, in particular the induction of VPS34 kinase by ULK1-mediated beclin 1 phosphorylation. The RBPs HNRNPQ and poly(A) binding protein nuclear 1 (PABPN1) form a regulatory network that controls the turnover of distinct autophagy-related (ATG) proteins. We also show that oculopharyngeal muscular dystrophy (OPMD) mutations engender a switch from autophagosome stimulation to autophagosome inhibition by impairing PABPN1 and HNRNPQ control of the level of ULK1. The overexpression of HNRNPQ in OPMD patient-derived cells rescues the defective autophagy in these cells. Our data reveal a regulatory mechanism of autophagy induction that is compromised by PABPN1 disease mutations, and may thus further contribute to their deleterious effects.
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)