| Autor: |
Takahashi T; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan., Nakano Y; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan., Onomoto K; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan., Murakami F; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan., Komori C; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan., Suzuki Y; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan., Yoneyama M; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan., Ui-Tei K; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan. |
| Abstrakt: |
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. |
