Proteomics

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Short duplex RNAs induce potent immunostimulation via Hoogsteen G-G base pairing-mediated dimerization


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Severe Acute Respiratory Syndrome

SUBMITTER: Tian Zhang  

LAB HEAD: Steven Gygi

PROVIDER: PXD027838 | Pride | 2022-09-01

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
TMT_Frac_1.mzIdentML Mzid
TMT_Frac_1.raw Raw
TMT_Frac_10.mzIdentML Mzid
TMT_Frac_10.raw Raw
TMT_Frac_11.mzIdentML Mzid
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