| Autor: |
Riccardo Guidi, Christopher Wedeles, Daqi Xu, Krzysztof Kolmus, Sarah E. Headland, Grace Teng, Joseph Guillory, Yi Jimmy Zeng, Tommy K. Cheung, Subhra Chaudhuri, Zora Modrusan, Yuxin Liang, Stuart Horswell, Benjamin Haley, Sascha Rutz, Christopher Rose, Yvonne Franke, Donald S. Kirkpatrick, Jason A. Hackney, Mark S. Wilson |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 12, Pp 113515- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.113515 |
| Popis: |
Summary: Argonaute (AGO) proteins execute microRNA (miRNA)-mediated gene silencing. However, it is unclear whether all 4 mammalian AGO proteins (AGO1, AGO2, AGO3, and AGO4) are required for miRNA activity. We generate Ago1, Ago3, and Ago4-deficient mice (Ago134Δ) and find AGO1/3/4 to be redundant for miRNA biogenesis, homeostasis, or function, a role that is carried out by AGO2. Instead, AGO1/3/4 regulate the expansion of type 2 immunity via precursor mRNA splicing in CD4+ T helper (Th) lymphocytes. Gain- and loss-of-function experiments demonstrate that nuclear AGO3 interacts directly with SF3B3, a component of the U2 spliceosome complex, to aid global mRNA splicing, and in particular the isoforms of the gene Nisch, resulting in a dysregulated Nisch isoform ratio. This work uncouples AGO1, AGO3, and AGO4 from miRNA-mediated RNA interference, identifies an AGO3:SF3B3 complex in the nucleus, and reveals a mechanism by which AGO proteins regulate inflammatory diseases. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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