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Protein products of nonstop mRNA disrupt nucleolar homeostasis.

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.

SUBMITTER: Davis ZH

PROVIDER: S-EPMC8065075 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Protein products of nonstop mRNA disrupt nucleolar homeostasis.

Davis Zoe H ZH Mediani Laura L Antoniani Francesco F Vinet Jonathan J Li Shuangxi S Alberti Simon S Lu Bingwei B Holehouse Alex S AS Carra Serena S Brandman Onn O

Cell stress & chaperones 20210222 3

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. Nucl ...[more]

PMID: 33619693

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