Protein products of nonstop mRNA disrupt nucleolar homeostasis

Cell Stress Chaperones. 2021 Feb 22. doi: 10.1007/s12192-021-01200-w. Online ahead of print.ABSTRACTStalled 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.PMID:33619693 | DOI:10.1007/s12192-021-01200-w

Source: Cell Stress and Chaperones - February 23, 2021 Category: Cytology Authors: Zoe H Davis Laura Mediani Francesco Antoniani Jonathan Vinet Shuangxi Li Simon Alberti Bingwei Lu Alex S Holehouse Serena Carra Onn Brandman Source Type: research