Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 17, Pages 9134-9147Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky575
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21310123, 21115004, 15H04319, 16H14640, 221S0002, 16H06279, 15K19124, 18K15178]
- Ichiro Kanehara Foundation
- Inamori Foundation
- Uehara Memorial Foundation
- Suzuken Memorial Foundation
- Japan Health & Research Institute
- Joint Research Center for Promotion of Basic and Applied Medical Sciences
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [21310123, 21115004, 15H04319, 18K15178, 15K19124] Funding Source: KAKEN
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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.
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