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

Nucleic Acids Res. 2018 Sep 28;46(17):9134-9147. doi: 10.1093/nar/gky575.


Here we show that laboratory of genetics and physiology 2 (LGP2) virus sensor protein regulates gene expression network of endogenous genes mediated by TAR-RNA binding protein (TRBP)-bound microRNAs (miRNAs). TRBP is an enhancer of RNA silencing, and functions to recruit precursor-miRNAs (pre-miRNAs) to Dicer that processes pre-miRNA into mature miRNA. Viral infection activates the antiviral innate immune response in mammalian cells. Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, melanoma-differentiation-associated gene 5 (MDA5), and LGP2, function as cytoplasmic virus sensor proteins during viral infection. RIG-I and MDA5 can distinguish between different types of RNA viruses to produce antiviral cytokines, including type I interferon. However, the role of LGP2 is controversial. We found that LGP2 bound to the double-stranded RNA binding sites of TRBP, resulting in inhibition of pre-miRNA binding and recruitment by TRBP. Furthermore, although it is unclear whether TRBP binds to specific pre-miRNA, we found that TRBP bound to particular pre-miRNAs with common structural characteristics. Thus, LGP2 represses specific miRNA activities by interacting with TRBP, resulting in selective regulation of target genes. Our findings show that a novel function of LGP2 is to modulate RNA silencing, indicating the crosstalk between RNA silencing and RLR signaling in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Gene Editing
  • Gene Expression Regulation / genetics
  • Gene Knockdown Techniques
  • Gene Regulatory Networks / genetics*
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • MicroRNAs / physiology
  • RNA Helicases / physiology*
  • RNA Interference
  • RNA Viruses / genetics
  • RNA Viruses / metabolism
  • RNA-Binding Proteins / metabolism*
  • RNA-Binding Proteins / physiology
  • Signal Transduction


  • MicroRNAs
  • RNA-Binding Proteins
  • trans-activation responsive RNA-binding protein
  • DHX58 protein, human
  • RNA Helicases