Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis

Hasan Ishtayeh, Margarita Galves, Tania T. Barnatan, Yevgeny Berdichevsky, Fatima Amer-Sarsour, Metsada Pasmanik-Chor, Itzhak Braverman, Sergiu C. Blumen, Avraham Ashkenazi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere13949
JournalAging Cell
Issue number10
StatePublished - Oct 2023


  • autophagy
  • autophagy genes
  • nutrient deprivation
  • trinucleotide repeat expansion


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