Protein products of nonstop mRNA disrupt nucleolar homeostasis

Zoe H. Davis; Laura Mediani; Francesco Antoniani; Jonathan Vinet; Shuangxi Li; Simon Alberti; Bingwei Lu; Alex S. Holehouse; Serena Carra; Onn Brandman

doi:10.1007/s12192-021-01200-w

Protein products of nonstop mRNA disrupt nucleolar homeostasis

Zoe H. Davis, Laura Mediani, Francesco Antoniani, Jonathan Vinet, Shuangxi Li, Simon Alberti, Bingwei Lu, Alex S. Holehouse, Serena Carra, Onn Brandman

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Pages (from-to)	549-561
Number of pages	13
Journal	Cell Stress and Chaperones
Volume	26
Issue number	3
DOIs	https://doi.org/10.1007/s12192-021-01200-w
State	Published - May 2021

Keywords

LTN1
Nonstop mRNA
Nucleolus
Phase separation
Protein quality control
Ribosome-associated quality control (RQC)

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10.1007/s12192-021-01200-w

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title = "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.",

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AU - Davis, Zoe H.

AU - Mediani, Laura

AU - Antoniani, Francesco

AU - Vinet, Jonathan

AU - Li, Shuangxi

AU - Alberti, Simon

AU - Lu, Bingwei

AU - Holehouse, Alex S.

AU - Carra, Serena

AU - Brandman, Onn

PY - 2021/5

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AB - 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.

KW - LTN1

KW - Nonstop mRNA

KW - Nucleolus

KW - Phase separation

KW - Protein quality control

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Protein products of nonstop mRNA disrupt nucleolar homeostasis

Abstract

Keywords

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