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Status |
Public on Mar 08, 2022 |
Title |
The RNA Helicase DHX16 Provides Specific Viral RNA for RIG-I to Trigger Innate Antiviral Immunity |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Type-I interferon (IFN-I) is essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses, however few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue and identified the DEAH-box RNA helicase DHX16 as a factor that enhances IFN-I production. Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3 Ub ligase TRIM6. DHX16 recognizes a signal in influenza segments that undergo splicing and requires its intact RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a potentiator of RIG-I-mediated IFN-I production and recognizes a mechanism for activation of antiviral immunity requiring unanchored poly-Ub and the viral RNA recognition activity of DHX16
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Overall design |
Next Generation Sequencing of human A549 lung cells treated with either non-targeting control or DHX16 targeting siRNA and either mock or influenza A virus infected (MOI=1) for 24 hours.
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Contributor(s) |
Hage A, Bharaj P, van Tol S, Giraldo MI, Aguilera-Aguirre L, Xie X, Widen SG, Moulton HM, Johnson JR, Krogan NJ, García-Sastre A, Shi P, Freiberg AN, Rajsbaum R |
Citation missing |
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Submission date |
Mar 04, 2021 |
Last update date |
Mar 08, 2022 |
Contact name |
Adam Hage |
Organization name |
University of Texas Medical Branch at Galveston
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Department |
Microbiology and Immunology
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Lab |
Rajsbaum Lab
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Street address |
301 University Blvd
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City |
Galveston |
State/province |
Texas |
ZIP/Postal code |
77555 |
Country |
USA |
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Platforms (1) |
GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
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Samples (8)
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Relations |
BioProject |
PRJNA706691 |
SRA |
SRP309315 |