PXD075151

PXD075151 is an original dataset announced via ProteomeXchange.

Title	Cytosolic interaction with RNA-helicase DDX39A titrates viral RNA G-quadruplex mediated α-Synuclein amyloidogenesis
Description	Amyloid aggregates of α-Synuclein are hallmark of Parkinson’s Disease (PD) and related neurodegenerative diseases. α-Synuclein, being an non-canonical RNA-binding protein (RBP), associates with other RBPs within cytosolic RNA-protein granules to modulate mRNA-stability. Conversely, mRNA G-quadruplexes (rG4s) expedite α-Synuclein amyloidogenesis. However, spatiotemporal control on α-Synuclein amyloidogenesis by other RBPs remains unexplored. Here, we report that RNA-dependent cytosolic interaction with DEAD-box RNA-helicase DDX39A decelerates α-Synuclein amyloidogenesis. Viral infections transiently elevate rG4s in cytoplasm. Perturbing interactions between α Synuclein and DDX39A using viral rG4s from H1N1-influenza and SARS-CoV-2 genomes expedites intracellular amyloidogenesis. Conversely, DDX39A overexpression alleviates α-Synuclein amyloidogenesis in mouse primary neurons triggered by SARS-CoV-2 infection. We demonstrate that while DDX39A unwinds viral rG4s to mitigate α-Synuclein sol-gel transition, its reciprocal cooperative phase separation with α-Synuclein enhances the helicase’s rG4-unwinding activity. We propose that accelerated α-Synuclein amyloidogenesis represents a trade-off within this RNA–protein interaction equilibrium, contributing to the viral etiology of PD.
HostingRepository	PRIDE
AnnounceDate	2026-09-05
AnnouncementXML	Submission_2026-09-05_05:40:08.297.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Swasti Raychaudhuri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-03 09:50:48	ID requested
⏵ 1	2026-09-05 05:40:08	announced

Dataset with its publication pending

submitter keyword: α-Synuclein, RNA G-quadruplex, DDX39A, viral infection, phase separation, amyloids

Swasti Raychaudhuri
contact affiliation	CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
contact email	rcswasti@ccmb.res.in
lab head
Swasti Raychaudhuri
contact affiliation	CSIR-Centre for Cellular and Molecular Biology
contact email	rcswasti@ccmb.res.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075151
     1. Label: PRIDE project
     2. Name: Cytosolic interaction with RNA-helicase DDX39A titrates viral RNA G-quadruplex mediated α-Synuclein amyloidogenesis