The role of UFMylation in ribosome quality control

/Abstract This research program explores how the ubiquitin-fold modifier 1 (UFM1) conjugation system orchestrates ribosome quality control (RQC) in mammalian cells. Our recent work has demonstrated that UFMylation spatially and temporally coordinates the disassembly and clearance of stalled ribosomes at the endoplasmic reticulum (ER), a process critical for maintaining translational fidelity and proteostasis. The proposed research will define the molecular basis by which UFMylation regulates ribosome recycling after normal termination and in response to collision-induced translational stalling. Using a multidisciplinary approach that includes genetics, biochemical reconstitution, cryo-electron microscopy, and ribosome profiling, we aim to delineate how UFMylation interfaces with canonical RQC pathways and adapts to cellular stress. The R35 mechanism will provide the flexibility to expand these foundational discoveries into new areas, including how dysregulation of this pathway may impact cell viability and stress resilience. Project Number: 1R35GM164167-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: RON KOPITO | Institution: STANFORD UNIVERSITY, STANFORD, CA | Award Amount: $285,031 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award - D Study Section[MRAD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11329548