PXD011728

PXD011728 is an original dataset announced via ProteomeXchange.

Title	Identification of Antiviral Roles for the Exon-Junction Complex and Nonsense-Mediated Decay in Flaviviral Infection
Description	West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (AP-MS) study to identify 259 WNV-interacting human proteins. RNAi screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor, PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral. Mechanistically, we found that the EJC protein RBM8A directly binds WNV RNA. To counteract this antiviral defense, flavivirus infection inhibits NMD and the interaction of capsid with PYM1 interferes with EJC protein function and localization. Moreover, depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC complex.
HostingRepository	PRIDE
AnnounceDate	2019-11-14
AnnouncementXML	Submission_2019-11-14_02:25:43.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-19 07:55:14	ID requested
⏵ 1	2019-11-14 02:37:30	announced

Li M, Johnson JR, Truong B, Kim G, Weinbren N, Dittmar M, Shah PS, Von Dollen J, Newton BW, Jang GM, Krogan NJ, Cherry S, Ramage H, Identification of antiviral roles for the exon-junction complex and nonsense-mediated decay in flaviviral infection. Nat Microbiol, 4(6):985-995(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Flavivirus, West Nile Virus, Nonsense-mediated decay, PYM1, exon-junction complex, virus-host interactions

Nevan J. Krogan
contact affiliation	University of California San Francisco
contact email	Nevan.Krogan@ucsf.edu
lab head
Jeffrey Johnson
contact affiliation	UCSF
contact email	jeffrey.johnson@ucsf.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/PXD011728

PRIDE project URI

• PRIDE
  1. PXD011728
     1. Label: PRIDE project
     2. Name: Identification of Antiviral Roles for the Exon-Junction Complex and Nonsense-Mediated Decay in Flaviviral Infection