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Updated: Nov 28, 2025
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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
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Human NLRP1 is a sensor for double-stranded RNA.
Stefan Bauernfried1, Matthias J Scherr2, Andreas Pichlmair3,4
1Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Science (New York, N.Y.)
|November 27, 2020
Summary
Human NLRP1 inflammasomes directly sense double-stranded RNA (dsRNA), a key component of RNA virus infection. This discovery reveals NLRP1
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Inflammasomes are critical intracellular sensors for pathogen detection and cellular stress, implicated in various diseases.
- NLRP1 inflammasomes are abundant in epithelial barrier tissues, suggesting a role in host defense.
- Semliki Forest virus (SFV) is a positive-strand RNA virus.
Purpose of the Study:
- To investigate the role of NLRP1 inflammasomes in sensing viral infections in keratinocytes.
- To identify specific viral components that trigger NLRP1 activation.
- To elucidate the molecular mechanism of NLRP1 inflammasome activation by RNA viruses.
Main Methods:
- Screening of a diverse viral panel for inflammasome activation in keratinocytes.
- Investigating the requirement of SFV replication and double-stranded RNA (dsRNA) formation for NLRP1 engagement.
- Biochemical analysis of NLRP1 binding to dsRNA and its enzymatic activity.
Main Results:
- Semliki Forest virus (SFV) potently activates human NLRP1, but not murine NLRP1B.
- SFV replication and the resultant formation of dsRNA are necessary for NLRP1 inflammasome activation.
- Delivery of long dsRNA alone is sufficient to trigger NLRP1 activation.
- NLRP1 directly binds dsRNA via its leucine-rich repeat domain, activating its NACHT domain's ATPase activity.
Conclusions:
- Human NLRP1 functions as a direct sensor for dsRNA.
- NLRP1 activation by dsRNA establishes its role in detecting RNA virus infections.
- These findings provide new insights into the innate immune response against RNA viruses.
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