Details:

Alternative Title:
Nature
Personal Author:
Arribere, Joshua A. ; Cenik, Elif S. ; Jain, Nimit ; Hess, Gaelen T. ; Lee, Cameron H. ; ... More +
Arribere, Joshua A. ; Cenik, Elif S. ; Jain, Nimit ; Hess, Gaelen T. ; Lee, Cameron H. ; Bassik, Michael C. ; Fire, Andrew Z. Less -
Description:
A fraction of ribosomes engaged in translation will fail to terminate when reaching a stop codon, yielding nascent proteins inappropriately extended on their C termini. Although such extended proteins can interfere with normal cellular processes, known mechanisms of translational surveillance are insufficient to protect cells from potential dominant consequences. Here, through a combination of transgenics and CRISPR–Cas9 gene editing in Caenorhabditis elegans, we demonstrate a consistent ability of cells to block accumulation of C-terminal-extended proteins that result from failure to terminate at stop codons. Sequences encoded by the 3′ untranslated region (UTR) were sufficient to lower protein levels. Measurements of mRNA levels and translation suggested a co- or post-translational mechanism of action for these sequences in C. elegans. Similar mechanisms evidently operate in human cells, in which we observed a comparable tendency for translated human 3′ UTR sequences to reduce mature protein expression in tissue culture assays, including 3′ UTR sequences from the hypomorphic ‘Constant Spring’ haemoglobin stop codon variant. We suggest that 3′ UTRs may encode peptide sequences that destabilize the attached protein, providing mitigation of unwelcome and varied translation errors.
Subject:
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3' Untranslated Regions Animals Animals, Genetically Modified Article Caenorhabditis Elegans Codon, Terminator CRISPR-Cas Systems Genes Hemoglobins, Abnormal Humans Peptides Protein Biosynthesis Proteins Ribosomes
Source:
Nature. 534(7609):719-723.
Pubmed ID:
27281202
Pubmed Central ID:
PMC5054982
Document Type:
Journal Article
Funding:
1DP2HD084069-01/DP/NCCDPHP CDC HHS/United States ; T32HG000044/HG/NHGRI NIH HHS/United States ; F32 GM112474/GM/NIGMS NIH HHS/United States ; R01GM37706/GM/NIGMS NIH HHS/United States ; 5F32GM112474-02/GM/NIGMS NIH HHS/United States ; ... More +
1DP2HD084069-01/DP/NCCDPHP CDC HHS/United States ; T32HG000044/HG/NHGRI NIH HHS/United States ; F32 GM112474/GM/NIGMS NIH HHS/United States ; R01GM37706/GM/NIGMS NIH HHS/United States ; 5F32GM112474-02/GM/NIGMS NIH HHS/United States ; R01 GM037706/GM/NIGMS NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:779fdfb1b10de65b00007276be704b8e561c808fcf47eea8e054b6e2daf12e79
Download URL:
https://stacks.cdc.gov/view/cdc/41676/cdc_41676_DS1.pdf
File Type:

Supporting Files

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