PXD037037 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mechanisms of stop codon readthrough mitigation reveal principles of GCN1 mediated translational quality control |
Description | Readthrough into the 3′ untranslated region (3′UTR) of the mRNA results in the production of aberrant proteins. Metazoans efficiently clear readthrough proteins, but the underlying mechanisms remain unknown. Here, we show in C. elegans and mammalian cells that readthrough proteins are targeted by a coupled, two-level quality control pathway involving the BAG6 chaperone complex and the ribosome collision-sensing protein GCN1. Readthrough proteins with hydrophobic C-terminal extensions are recognized by SGTA-BAG6 and ubiquitylated by RNF126 for proteasomal degradation. Additionally, cotranslational mRNA decay initiated by GCN1 and CCR4/NOT limits the accumulation of readthrough products. Unexpectedly, selective ribosome profiling uncovered a general role of GCN1 in regulating translation dynamics when ribosomes encounter nonoptimal codons, a feature of 3′UTR sequences. Dysfunction of GCN1 results in mRNA and proteome imbalance, increasingly perturbing transmembrane proteins and collagens during aging. These results define GCN1 as a key factor acting during translation in maintaining protein homeostasis. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:47:32.865.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Martin Mueller |
SpeciesList | scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-27 11:31:06 | ID requested | |
1 | 2023-06-09 05:02:16 | announced | |
⏵ 2 | 2024-10-22 05:47:33 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: HEK293 C.elegans |
Contact List
Ulrich Hartl |
contact affiliation | MPI of Biochemistry |
contact email | uhartl@biochem.mpg.de |
lab head | |
Martin Mueller |
contact affiliation | MPI of Biochemistry |
contact email | mamueller@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037037
- Label: PRIDE project
- Name: Mechanisms of stop codon readthrough mitigation reveal principles of GCN1 mediated translational quality control