Ubiquitination of stalled ribosomes enables mRNA decay via HBS-1 and NONU-1 in vivo.
Autor: | Monem PC; Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California, United States of America., Vidyasagar N; Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California, United States of America., Piatt AL; Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California, United States of America., Sehgal E; Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California, United States of America., Arribere JA; Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California, United States of America. |
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Jazyk: | angličtina |
Zdroj: | PLoS genetics [PLoS Genet] 2023 Jan 10; Vol. 19 (1), pp. e1010577. Date of Electronic Publication: 2023 Jan 10 (Print Publication: 2023). |
DOI: | 10.1371/journal.pgen.1010577 |
Abstrakt: | As ribosomes translate the genetic code, they can encounter a variety of obstacles that hinder their progress. If ribosomes stall for prolonged times, cells suffer due to the loss of translating ribosomes and the accumulation of aberrant protein products. Thus to protect cells, stalled ribosomes experience a series of reactions to relieve the stall and degrade the offending mRNA, a process known as No-Go mRNA Decay (NGD). While much of the machinery for NGD is known, the precise ordering of events and factors along this pathway has not been tested. Here, we deploy C. elegans to unravel the coordinated events comprising NGD. Utilizing a novel reporter and forward and reverse genetics, we identify the machinery required for NGD. Our subsequent molecular analyses define a functional requirement for ubiquitination on at least two ribosomal proteins (eS10 and uS10), and we show that ribosomes lacking ubiquitination sites on eS10 and uS10 fail to perform NGD in vivo. We show that the nuclease NONU-1 acts after the ubiquitin ligase ZNF-598, and discover a novel requirement for the ribosome rescue factors HBS-1/PELO-1 in mRNA decay via NONU-1. Taken together, our work demonstrates mechanisms by which ribosomes signal to effectors of mRNA repression, and we delineate links between repressive factors working toward a well-defined NGD pathway. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Monem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
Databáze: | MEDLINE |
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