PXD013834

PXD013834 is an original dataset announced via ProteomeXchange.

Title	Chemical damage to mRNA triggers ribosome-based quality control in the cell
Description	Maintaining the integrity of nucleic acids is an essential feature of all organisms. Unwanted modification of DNA, if left unrepaired, is deleterious to cellular homeostasis and could have far-reaching consequences that include genomic instability and accumulation of mutations. Similarly, accumulation of damaged RNA has been correlated with various neurodegenerative diseases. Given their inherent reactivity, nucleic acids are susceptible to damage from both endogenous and exogenous reactive oxygen species (ROS) as well as alkylation agents. We have recently begun to address how some of these modifications on mRNA impact the function of the ribosome and in particular the decoding process. We find that most modifications severely change the speed and accuracy of translation. These observations revealed that oxidation of RNA is most likely to stall the ribosome and necessitates the presence of quality-control processes to handle damaged mRNA. To this end, we have uncovered a connection between the process of no-go decay (NGD), which degrades mRNAs that stall translation, and chemical insults. In the absence of key NGD factors in yeast, the levels of damaged mRNA significantly increase and cells are rendered sensitive to oxidizing and alkylation agents. Furthermore, these agents activate ribosome quality control (RQC) of nascent peptides. Deletion of the E3 ligase responsible for the ubiquitination of the nascent peptides resulted in the accumulation of protein aggregates in the presence of oxidizing and alkylating agents. These observations suggest that chemical damage stalls translation, activating NGD and RQC. Interestingly, the addition of nucleic-acids-damaging agents was also found to result in K63-linked ubiquitination of ribosomal proteins. This signaling-mode of ubiquitination precedes DNA-damage marks, indicating that cells respond to RNA damage due to stalled ribosomes before DNA damage. Collectively our data highlights the burden of chemically-damaged mRNA on cellular homeostasis and suggests that organisms evolved ribosome-based mRNA-surveillance processes to rapidly degrade it.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:54:36.902.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fionn McLoughlin
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	ubiquitination signature dipeptidyl lysine; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-14 02:13:20	ID requested
1	2019-11-06 23:42:53	announced
2	2020-01-13 05:29:08	announced	2020-01-13: Updated publication reference for PubMed record(s): 31819057.
⏵ 3	2024-10-22 04:54:37	announced	2024-10-22: Updated project metadata.

Yan LL, Simms CL, McLoughlin F, Vierstra RD, Zaher HS, Oxidation and alkylation stresses activate ribosome-quality control. Nat Commun, 10(1):5611(2019) [pubmed]

10.1038/s41467-019-13579-3;

submitter keyword: ubiquitylation, quality control,Ribosome collision

Hani Zaher
contact affiliation	Biology department, Washington University in St Louis, MO, USA
contact email	hzaher@wustl.edu
lab head
Fionn McLoughlin
contact affiliation	Washington University in Saint Louis
contact email	fmcloughlin@wustl.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD013834

PRIDE project URI

• PRIDE
  1. PXD013834
     1. Label: PRIDE project
     2. Name: Chemical damage to mRNA triggers ribosome-based quality control in the cell