DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling

Area of Science:

• Molecular Biology
• Immunology
• Virology

Background:

• DEAD-box RNA helicase 21 (DDX21) is an ATP-dependent RNA helicase involved in RNA processing and innate immunity.
• Its precise role in type I interferon (IFN-I) production, whether inductive or antagonistic, remains unclear.
• Previous studies relied on overexpression or knockdown, necessitating further investigation.

Purpose of the Study:

• To elucidate the role of DDX21 in regulating type I interferon (IFN-I) production.
• To investigate the mechanism by which DDX21 influences IFN-I signaling pathways.
• To identify specific domains of DDX21 involved in its immune regulatory function.

Main Methods:

• Generation of DDX21 knockout cell lines.
• Stimulation with Sendai virus (SeV) to induce IFN-β production.
• Analysis of IFN-β and IFN-stimulated gene (ISG) expression.
• Investigation of DDX21's interaction with double-stranded RNA (dsRNA) and RIG-I.

Main Results:

• DDX21 knockout cells exhibited enhanced Sendai virus-induced IFN-β production and ISG expression.
• DDX21 was identified as a negative regulator of IFN-β production.
• DDX21 competes with RIG-I for dsRNA binding, thereby attenuating RIG-I-mediated IFN-β production.
• The 217-784 amino acid region of DDX21 is crucial for dsRNA binding and antagonistic activity.

Conclusions:

• DDX21 functions as a negative regulator of type I interferon production.
• DDX21 antagonizes RIG-I-mediated antiviral signaling by competing for dsRNA.
• DDX21 plays a critical role in maintaining immune homeostasis by dampening excessive inflammatory responses.