Argonaute3-SF3B3 complex controls pre-mRNA splicing to restrain type 2 immunity

被引：1

作者：

Guidi, Riccardo ^{[1
]}

Wedeles, Christopher ^{[1
]}

Xu, Daqi ^{[1
]}

Kolmus, Krzysztof ^{[2
]}

Headland, Sarah E. ^{[1
]}

Teng, Grace ^{[1
]}

Guillory, Joseph ^{[3
]}

Zeng, Yi Jimmy ^{[4
]}

Cheung, Tommy K. ^{[4
]}

Chaudhuri, Subhra ^{[3
]}

Modrusan, Zora ^{[3
]}

Liang, Yuxin ^{[3
]}

Horswell, Stuart ^{[5
]}

Haley, Benjamin ^{[6
]}

Rutz, Sascha ^{[7
]}

Rose, Christopher ^{[4
]}

Franke, Yvonne ^{[8
]}

Kirkpatrick, Donald S. ^{[4
]}

Hackney, Jason A. ^{[2
]}

Wilson, Mark S. ^{[1
]}

机构：

[1] Genentech Inc, Immunol Discovery, South San Francisco, CA 94080 USA

[2] Genentech Inc, OMNI Bioinformat, South San Francisco, CA 94080 USA

[3] Genentech Inc, Next Generat Sequencing NGS, San Francisco, CA 94080 USA

[4] Genentech Inc, Microchem Prote & Lipid, South San Francisco, CA 94080 USA

[5] Francis Crick Inst, Bioinformat & Biostat, London, England

[6] Genentech Inc, Mol Biol, South San Francisco, CA 94080 USA

[7] Genentech Inc, Canc Immunol, South San Francisco, CA 94080 USA

[8] Genentech Inc, Prot Sci, South San Francisco, CA 94080 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 12期

基金：

欧盟地平线“2020”;

关键词：

MAMMALIAN MICRORNAS; DISTINCT ROLES; PROTEINS; DICER; IDENTIFICATION; CELLS; METABOLISM; REPRESSION; REVEALS; FAMILY;

D O I：

10.1016/j.celrep.2023.113515

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (Ago134D) 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 miRNAmediated RNA interference, identifies an AGO3:SF3B3 complex in the nucleus, and reveals a mechanism by which AGO proteins regulate inflammatory diseases.

引用

页数：19

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