Abstract:
:Cells continuously monitor protein synthesis to prevent accumulation of aberrant polypeptides. Insufficient capacity of cellular degradative systems, chaperone shortage or high levels of mistranslation by ribosomes can result in proteotoxic stress and endanger proteostasis. One of the least explored reasons for mistranslation is the incorrect functioning of the ribosome itself. To understand how cells deal with ribosome malfunction, we introduced mutations in the Expansion Segment 7 (ES7L) of 25S rRNA that allowed the formation of mature, translationally active ribosomes but induced proteotoxic stress and compromised cell viability. The ES7L-mutated ribosomes escaped nonfunctional rRNA Decay (NRD) and remained stable. Remarkably, ES7L-mutated ribosomes showed increased segregation into cytoplasmic foci containing soluble misfolded proteins. This ribosome entrapment pathway, termed TRAP (Translational Relocalization with Aberrant Polypeptides), was generalizable beyond the ES7L mutation, as wild-type ribosomes also showed increased relocalization into the same compartments in cells exposed to proteotoxic stressors. We propose that during TRAP, assembled ribosomes associated with misfolded nascent chains move into cytoplasmic compartments enriched in factors that facilitate protein quality control. In addition, TRAP may help to keep translation at its peak efficiency by preventing malfunctioning ribosomes from active duty in translation.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Ghosh A,Williams LD,Pestov DG,Shcherbik Ndoi
10.1093/nar/gkaa068subject
Has Abstractpub_date
2020-04-17 00:00:00pages
3888-3905issue
7eissn
0305-1048issn
1362-4962pii
5728877journal_volume
48pub_type
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