PXD037037-1

PXD037037 is an original dataset announced via ProteomeXchange.

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	2023-06-09
AnnouncementXML	Submission_2023-06-09_05:02:16.079.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MartinMueller
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

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.

Dataset with its publication pending

submitter keyword: HEK293 C.elegans

UlrichHartl
contact affiliation	MPI of Biochemistry
contact email	uhartl@biochem.mpg.de
lab head
MartinMueller
contact affiliation	MPI of Biochemistry
contact email	mamueller@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037037
     1. Label: PRIDE project
     2. Name: Mechanisms of stop codon readthrough mitigation reveal principles of GCN1 mediated translational quality control