PXD027838

PXD027838 is an original dataset announced via ProteomeXchange.

Title	Short duplex RNAs induce potent immunostimulation via Hoogsteen G-G base pairing-mediated dimerization
Description	Here we describe a new class of immunostimulatory short duplex RNAs that potently induce production of type I interferon (IFN-I), and particularly IFN-β, in a wide range ofhuman cell types via end-to-end dimerization, direct binding to RIG-I, and activation of the RIG-I/IRF3 pathway. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates the self-assembly of end-to-end RNA dimers by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases also did not affect their ability to induce IFN-I production. Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in cell lines and in human Lung Chips that mimic organlevel lung pathophysiology. These novel immunostimulatory motifs potentially could be harnessed to create broad-spectrum antiviral therapeutics, but they should be avoided when designing siRNAs to minimize immunological side effects.
HostingRepository	PRIDE
AnnounceDate	2022-09-01
AnnouncementXML	Submission_2022-09-01_12:50:52.003.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tian Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-10 00:00:18	ID requested
⏵ 1	2022-09-01 12:50:52	announced

10.1016/J.OMTN.2022.08.031;

submitter keyword: Short duplex RNA, Immune stimulation, Type I interferon, Lung chips, SARS-CoV-2

Steven Gygi
contact affiliation	Cell Biology Department, Harvard Medical School
contact email	steven_gygi@hms.harvard.edu
lab head
Tian Zhang
contact affiliation	Harvard Medical School
contact email	tian_zhang@hms.harvard.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/2022/09/PXD027838

PRIDE project URI

• PRIDE
  1. PXD027838
     1. Label: PRIDE project
     2. Name: Short duplex RNAs induce potent immunostimulation via Hoogsteen G-G base pairing-mediated dimerization