| First Author | Choi JH | Year | 2020 |
| Journal | Genes Dev | Volume | 34 |
| Issue | 23-24 | Pages | 1697-1712 |
| PubMed ID | 33184222 | Mgi Jnum | J:299452 |
| Mgi Id | MGI:6490027 | Doi | 10.1101/gad.340604.120 |
| Citation | Choi JH, et al. (2020) DUSP11-mediated control of 5'-triphosphate RNA regulates RIG-I sensitivity. Genes Dev 34(23-24):1697-1712 |
| abstractText | Deciphering the mechanisms that regulate the sensitivity of pathogen recognition receptors is imperative to understanding infection and inflammation. Here we demonstrate that the RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) acts on both host and virus-derived 5'-triphosphate RNAs rendering them less active in inducing a RIG-I-mediated immune response. Reducing DUSP11 levels alters host triphosphate RNA packaged in extracellular vesicles and induces enhanced RIG-I activation in cells exposed to extracellular vesicles. Virus infection of cells lacking DUSP11 results in a higher proportion of triphosphorylated viral transcripts and attenuated virus replication, which is rescued by reducing RIG-I expression. Consistent with the activity of DUSP11 in the cellular RIG-I response, mice lacking DUSP11 display lower viral loads, greater sensitivity to triphosphorylated RNA, and a signature of enhanced interferon activity in select tissues. Our results reveal the importance of controlling 5'-triphosphate RNA levels to prevent aberrant RIG-I signaling and demonstrate DUSP11 as a key effector of this mechanism. |
