論文 - 詳細
| RRC ID | 86115 |
|---|---|
| 著者 | Onomoto K, Sakai M, Watanabe M, Fukao A, Sakamura Y, Miyao M, Tomohiro T, Yamashita A, Fujiwara T, Takahashi T, Ui-Tei K, Yoneyama M. |
| タイトル | TRBP modulates RLR signaling by inhibiting PKR-mediated antiviral stress granule formation. |
| ジャーナル | Sci Rep |
| Abstract |
Stress granules (SGs) are dense aggregates of RNA and proteins that form in response to various cellular stresses. Virus-induced SGs, known as antiviral SGs (avSGs), play a crucial role in regulating retinoic acid-inducible gene I-like receptors (RLRs)-mediated antiviral innate immunity. However, the regulation of avSG formation remains not fully understood. In this study, we demonstrate that TAR-RNA binding protein (TRBP), an RNA silencing regulator, negatively regulates type I interferon (IFN) expression by inhibiting avSG formation in response to RNA virus infection. Overexpression of TRBP inhibits both IFN-β promoter activity and avSG formation following viral infection or the viral RNA mimic, polyinosinic-polycytidylic acid transfection. TRBP knockout cells exhibit enhanced phosphorylation and activation of IFN regulatory factor-3 (IRF-3) and increased IFN-β mRNA expression compared to wild-type cells. Additionally, depletion of G3BP1 and G3BP2, which are essential for SG formation, abolishes the inhibitory effect of TRBP on IRF-3 phosphorylation. Mechanistically, TRBP physically interacts with double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), a key kinase involved in avSG formation, via its dsRNA-binding domains, and inhibits PKR activation. In summary, our findings reveal a novel function for TRBP as a negative regulator of RLR-mediated signaling through PKR-dependent inhibition of avSG formation. |
| 巻・号 | 15(1) |
| ページ | 20678 |
| 公開日 | 2025-7-1 |
| DOI | 10.1038/s41598-025-07121-3 |
| PII | 10.1038/s41598-025-07121-3 |
| PMID | 40593223 |
| PMC | PMC12215557 |
| MeSH | Adaptor Proteins, Signal Transducing DEAD Box Protein 58 / metabolism DNA Helicases / genetics DNA Helicases / metabolism HEK293 Cells Humans Immunity, Innate Interferon Regulatory Factor-3 / metabolism Interferon-beta / genetics Interferon-beta / metabolism Phosphorylation Poly-ADP-Ribose Binding Proteins / genetics Poly-ADP-Ribose Binding Proteins / metabolism RNA Helicases / genetics RNA Helicases / metabolism RNA Recognition Motif Proteins / genetics RNA Recognition Motif Proteins / metabolism RNA Virus Infections RNA-Binding Proteins* / genetics RNA-Binding Proteins* / metabolism Signal Transduction* Stress Granules* / metabolism eIF-2 Kinase* / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |