Protein products of nonstop mRNA disrupt nucleolar homeostasis.

Autor: Davis ZH; Department of Biochemistry, Stanford University, Stanford, CA, 94305, USA., Mediani L; Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio, Emilia, Modena, Italy., Antoniani F; Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio, Emilia, Modena, Italy., Vinet J; Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio, Emilia, Modena, Italy., Li S; Department of Pathology, Stanford University, Stanford, CA, 94305, USA., Alberti S; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universitat Dresden, Tatzberg 47/49, 01307, Dresden, Germany., Lu B; Department of Pathology, Stanford University, Stanford, CA, 94305, USA., Holehouse AS; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.; Center for Science and Engineering of Living Systems (CSELS), Washington University in St. Louis, St. Louis, MO, 63130, USA., Carra S; Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio, Emilia, Modena, Italy. serena.carra@unimore.it., Brandman O; Department of Biochemistry, Stanford University, Stanford, CA, 94305, USA. onn@stanford.edu.
Jazyk: angličtina
Zdroj: Cell stress & chaperones [Cell Stress Chaperones] 2021 May; Vol. 26 (3), pp. 549-561. Date of Electronic Publication: 2021 Feb 22.
DOI: 10.1007/s12192-021-01200-w
Abstrakt: Stalled mRNA translation results in the production of incompletely synthesized proteins that are targeted for degradation by ribosome-associated quality control (RQC). Here we investigated the fate of defective proteins translated from stall-inducing, nonstop mRNA that escape ubiquitylation by the RQC protein LTN1. We found that nonstop protein products accumulated in nucleoli and this localization was driven by polylysine tracts produced by translation of the poly(A) tails of nonstop mRNA. Nucleolar sequestration increased the solubility of invading proteins but disrupted nucleoli, altering their dynamics, morphology, and resistance to stress in cell culture and intact flies. Our work elucidates how stalled translation may affect distal cellular processes and may inform studies on the pathology of diseases caused by failures in RQC and characterized by nucleolar stress.
Databáze: MEDLINE