| Literature DB >> 33619693 |
Zoe H Davis1, Laura Mediani2, Francesco Antoniani2, Jonathan Vinet2, Shuangxi Li3, Simon Alberti4, Bingwei Lu3, Alex S Holehouse5,6, Serena Carra7, Onn Brandman8.
Abstract
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.Entities:
Keywords: LTN1; Nonstop mRNA; Nucleolus; Phase separation; Protein quality control; Ribosome-associated quality control (RQC)
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Year: 2021 PMID： 33619693 PMCID： PMC8065075 DOI： 10.1007/s12192-021-01200-w
Source DB: PubMed Journal: Cell Stress Chaperones ISSN： 1355-8145 Impact factor: 3.667