LGP2 virus sensor regulates gene expression network mediated by TRBP-bound microRNAs

Area of Science:

• Molecular Biology
• Immunology
• Virology

Background:

• Viral infection triggers innate immune responses in mammalian cells via Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs).
• RLRs, including RIG-I, MDA5, and LGP2, act as cytoplasmic sensors for viral RNA.
• The precise role of LGP2 in antiviral responses and its interaction with RNA silencing pathways remains incompletely understood.

Purpose of the Study:

• To elucidate the function of LGP2 in regulating gene expression through microRNA (miRNA) pathways.
• To investigate the interaction between LGP2, TAR-RNA binding protein (TRBP), and miRNA processing.
• To understand the crosstalk between RNA silencing and RLR signaling during viral infections.

Main Methods:

• Investigated the interaction between LGP2 and TRBP using molecular binding assays.
• Analyzed the effect of LGP2 on the recruitment of precursor-miRNAs (pre-miRNAs) by TRBP.
• Characterized the binding specificity of TRBP to pre-miRNAs with specific structural features.

Main Results:

• LGP2 binds to the double-stranded RNA binding sites of TRBP, inhibiting pre-miRNA binding and recruitment.
• TRBP selectively binds to pre-miRNAs possessing common structural characteristics.
• LGP2 represses specific miRNA activities by modulating TRBP interactions, leading to selective gene regulation.

Conclusions:

• LGP2 plays a novel role in modulating RNA silencing pathways by interacting with TRBP.
• This interaction selectively regulates miRNA activity and downstream gene expression.
• Findings highlight a significant crosstalk between RNA silencing and RLR signaling in mammalian antiviral defense.