Translation-dependent unwinding of stem–loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs
| Autor: | Tomoko Emura, Akio Yamashita, Kumi Hidaka, Osamu Takeuchi, Noriki Iwai, Kentaro Inoue, Hiroshi Sugiyama, Kotaro Akaki, Fabian Hia, Takuya Uehata, Mariko Okada-Hatakeyama, Shigeo Ohno, Takashi Mino, Masayuki Endo, Yutaka Suzuki, Daron M. Standley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
RNase P
Primary Cell Culture Plasma protein binding Biology Protein Serine-Threonine Kinases 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Ribonucleases Genetics Protein biosynthesis RNA and RNA-protein complexes Animals Homeostasis Humans Protein Interaction Domains and Motifs RNA Messenger 030304 developmental biology Inflammation Mice Knockout 0303 health sciences Messenger RNA Innate immune system Macrophages Inverted Repeat Sequences RNA Fibroblasts Immunity Innate Single Molecule Imaging Cell biology Nonsense Mediated mRNA Decay HEK293 Cells chemistry Protein Biosynthesis Mutation Macrophages Peritoneal Trans-Activators 030217 neurology & neurosurgery Cytokinesis DNA HeLa Cells Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 0305-1048 |
| Popis: | Regnase-1-mediated mRNA decay (RMD), in which inflammatory mRNAs harboring specific stem–loop structures are degraded, is a critical part of proper immune homeostasis. Prior to initial translation, Regnase-1 associates with target stem–loops but does not carry out endoribonucleolytic cleavage. Single molecule imaging revealed that UPF1 is required to first unwind the stem–loops, thus licensing Regnase-1 to proceed with RNA degradation. Following translation, Regnase-1 physically associates with UPF1 using two distinct points of interaction: The Regnase-1 RNase domain binds to SMG1-phosphorylated residue T28 in UPF1; in addition, an intrinsically disordered segment in Regnase-1 binds to the UPF1 RecA domain, enhancing the helicase activity of UPF1. The SMG1-UPF1–Regnase-1 axis targets pioneer rounds of translation and is critical for rapid resolution of inflammation through restriction of the number of proteins translated by a given mRNA. Furthermore, small-molecule inhibition of SMG1 prevents RNA unwinding in dendritic cells, allowing post-transcriptional control of innate immune responses. 炎症が制御される新たなRNA分解メカニズムを解明 --新たな免疫賦活化法の開発に道筋--. 京都大学プレスリリース. 2019-07-25. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|