PXD039981

PXD039981 is an original dataset announced via ProteomeXchange.

Title	Nsp1 guides ribosomal start site selection to promote SARS-CoV-2 infection
Description	Host-directed antivirals remain a promising therapeutic approach for many viruses, including SARS-CoV-2 (CoV2), but development of such interventions requires a deeper understanding of virus-host interactions. Here, we use subcellular proteomics to detect CoV2-induced changes in host protein synthesis networks. We identify molecular chaperones required for CoV2 infection and show that their inhibition reduces infection without major toxicity. We also find that the untranslated regions of CoV2 genomic RNA (gRNA) are inefficient drivers of translation initiation, and that the viral non-structural protein Nsp1 suppresses cellular mRNA but enhances viral gRNA translation. Nsp1 preferentially interacts with pre-initiation complexes containing translation factor EIF1A, which is required for accurate start site selection on CoV2 gRNA. Without EIF1A, more ribosomes initiate translation from an alternative start codon, resulting in lower Orf1 translation and reduced viral titers. Together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and identifies druggable targets for antiviral development.
HostingRepository	PRIDE
AnnounceDate	2024-01-12
AnnouncementXML	Submission_2024-01-12_14:58:13.215.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ranen Aviner
SpeciesList	scientific name: Cercopithecus aethiops (Green monkey) (Grivet); NCBI TaxID: 9534;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-09 00:57:35	ID requested
⏵ 1	2024-01-12 14:58:13	announced

Dataset with its publication pending

submitter keyword: SARS-CoV-2, ribosomes, proteostasis, LC-MS/MS, translation

Ranen Aviner
contact affiliation	Chan Zuckerberg Biohub San Francisco
contact email	ranen.aviner@czbiohub.org
lab head
Ranen Aviner
contact affiliation	Chan Zuckerberg Biohub
contact email	ranen.aviner@gmail.com
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/2024/01/PXD039981

PRIDE project URI

• PRIDE
  1. PXD039981
     1. Label: PRIDE project
     2. Name: Nsp1 guides ribosomal start site selection to promote SARS-CoV-2 infection