LGP2 virus sensor regulates gene expression network mediated by TRBP-bound microRNAs.
Nucleic Acids Res, 2018/09/28;46(17):9134-9147.
Takahashi T[1], Nakano Y[1], Onomoto K[2], Murakami F[3], Komori C[1], Suzuki Y[3], Yoneyama M[2], Ui-Tei K[1, 3]
Affiliations
PMID: 29939295DOI: 10.1093/nar/gky575
Impact factor: 19.16
Abstract
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.
MeSH terms
CRISPR-Cas Systems; Gene Editing; Gene Expression Regulation; Gene Knockdown Techniques; Gene Regulatory Networks; HeLa Cells; Humans; MicroRNAs; RNA Helicases; RNA Interference; RNA Viruses; RNA-Binding Proteins; Signal Transduction
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