PXD083784-1

PXD083784 is an original dataset announced via ProteomeXchange.

Title	Zika virus subverts the host m⁶A writer machinery to reprogram RNA fate during neurodevelopment
Description	Zika virus (ZIKV) infection causes congenital neurodevelopmental abnormalities, including microcephaly, yet how ZIKV alters post-transcriptional gene regulation during human brain development remains unclear. Here, we integrate virus–host interactomics, reverse genetics, m⁶A profiling, and human brain organoid models to investigate ZIKV regulation of the host m⁶A machinery. We find that the ZIKV envelope protein (E) interacts with METTL3, promoting its cytoplasmic redistribution and disrupting METTL3-METTL14 complex formation, thereby remodeling host m⁶A methylation. Transcriptome-wide analyses further indicate that these m⁶A changes are associated with altered RNA stability among transcripts linked to neurodevelopmental processes and immune-response pathways. Structure–function analysis identifies Asn238 of ZIKV-E as a key determinant of METTL3 interaction. A recombinant ZIKV-N238A mutant exhibits comparable replication kinetics but reduced METTL3 binding and relocalization. In human brain organoids, N238A partially attenuates ZIKV-induced cortical abnormalities, while analyses in neural progenitor and microglial cells show reduced effects on m⁶A enrichment and RNA stability. Together, these findings suggest that ZIKV-mediated disruption of METTL3-dependent m⁶A regulation contributes to neurodevelopmental defects by reprogramming transcript-specific RNA fate.
HostingRepository	iProX
AnnounceDate	2026-09-05
AnnouncementXML	Submission_2026-09-07_01:38:49.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ying Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-09-07 01:38:19	ID requested
⏵ 1	2026-09-07 01:38:49	announced

Dataset with its publication pending

submitter keyword: Zika virus E protein, Homo sapiens

Ying Wu
contact affiliation	Wuhan University
contact email	yingwu@whu.edu.cn
lab head
Ying Wu
contact affiliation	Wuhan University
contact email	yingwu@whu.edu.cn
dataset submitter

iProX dataset URI