Argonaute3-SF3B3 complex controls pre-mRNA splicing to restrain type 2 immunity.
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.
Pubmed ID: 38096048 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Anti-TARBP2 (RRID:AB_10620144)
- Anti-SF3B3 polyclonal antibody (RRID:AB_10960386)
- Anti-DDX1 antibody produced in rabbit (RRID:AB_10794321)
- Anti-CPSF3 antibody produced in rabbit (RRID:AB_10669728)
- Biotin anti-mouse/human KLRG1 (MAFA) (RRID:AB_10578565)
- Biotin anti-mouse CD115 (CSF-1R) (RRID:AB_2028401)
- Biotin anti-mouse CD103 (RRID:AB_535947)
- Biotin anti-mouse CD135 (RRID:AB_1953267)
- Biotin anti-mouse CD127 (IL-7Ralpha) (RRID:AB_2126118)
- APC anti-mouse CD93 (AA4.1, early B lineage) (RRID:AB_2275879)
- Purified anti-mouse CD117 (c-kit) Recombinant (RRID:AB_2734232)
- Alexa Fluor(R) 488 anti-mouse Ly-6G (RRID:AB_2561340)
- Alexa Fluor(R) 488 anti-mouse Ly-6C (RRID:AB_10640820)
- Biotin anti-mouse Ly-6A/E (Sca-1) (RRID:AB_313340)
- Pacific Blue anti-mouse Lineage Cocktail (RRID:AB_11150779)
- CD279 (PD-1) Monoclonal Antibody (J43), FITC, eBioscience (RRID:AB_465472)
- IL-13 Monoclonal Antibody (eBio13A), PE, eBioscience (RRID:AB_763559)
- Alexa Fluor(R) 488 anti-mouse IFN-gamma (RRID:AB_493312)
- Purified anti-mouse/human IL-5 (RRID:AB_315326)
- Purified anti-mouse IL-4 (RRID:AB_315316)
- Alexa Fluor(R) 488 anti-mouse I-A/I-E (RRID:AB_493523)
- Ms Siglec-F Biotin E50-2440 100ug (RRID:AB_2916663)
- FOXP3 Monoclonal Antibody (FJK-16s), PE, eBioscience (RRID:AB_465936)
- APC anti-mouse CD278 (ICOS) (RRID:AB_2728129)
- Purified anti-mouse CD86 (RRID:AB_313145)
- Biotin anti-mouse CD80 (RRID:AB_313125)
- Purified anti-mouse CD64 (FcgammaRI) (RRID:AB_10613107)
- Biotin anti-mouse CD63 (RRID:AB_2860698)
- Purified anti-mouse CD69 (RRID:AB_313105)
- Purified anti-mouse CD62L (RRID:AB_313089)
- Biotin anti-mouse CD49b (pan-NK cells) (RRID:AB_313411)
- Alexa Fluor(R) 488 anti-mouse/human CD45R/B220 (RRID:AB_389308)
- Pacific Blue(TM) anti-mouse CD45.2 (RRID:AB_492873)
- Biotin anti-mouse CD45.1 (RRID:AB_313492)
- CD45 Monoclonal Antibody (30-F11), eBioscience (RRID:AB_467251)
- CD44 Monoclonal Antibody (IM7), PE, eBioscience (RRID:AB_465664)
- Biotin anti-mouse CD25 (RRID:AB_312853)
- APC anti-mouse TCR beta chain (RRID:AB_313435)
- CD19 Monoclonal Antibody (eBio1D3 (1D3)), FITC, eBioscience (RRID:AB_657666)
- Purified anti-mouse CD16/32 (RRID:AB_312801)
- Purified anti-mouse CD11c Recombinant (RRID:AB_2876575)
- Biotin anti-mouse/human CD11b (RRID:AB_312786)
- CD8a Monoclonal Antibody (53-6.7), FITC, eBioscience (RRID:AB_464915)
- CD3 Monoclonal Antibody (17A2), eBioscience (RRID:AB_467053)
- Purified anti-mouse CD4 (RRID:AB_312708)
- GAPDH (D16H11) XP Rabbit mAb (RRID:AB_10622025)
- Lamin A/C Antibody (RRID:AB_2136278)
- c-Myc (D84C12) Rabbit mAb (Alexa Fluor® 647 Conjugate) (RRID:AB_2798334)
- Histone H3 antibody [mAbcam 10799] - ChIP Grade (RRID:AB_470239)
- Rabbit anti-SF3B5 Antibody, Affinity Purified (RRID:AB_2891502)
- SF3B1 (D7L5T) Rabbit mAb (RRID:AB_2798479)
- Mouse Anti-Human PHF5A Monoclonal, Unconjugated, Clone 2h7 (RRID:AB_2165366)
- Anti-XPO5 antibody produced in rabbit (RRID:AB_1848330)
- Recombinant Anti-SF3B3 antibody [EPR18440] (RRID:AB_2910146)
- HSP90 Antibody (RRID:AB_2121214)
- Mouse Anti-GW182 Monoclonal Antibody, Unconjugated, Clone 4B6 (RRID:AB_1310295)
- GW182 Polyclonal Antibody (RRID:AB_2780472)
- GW182 antibody (RRID:AB_10866284)
- EDC4/Ge-1 Antibody (RRID:AB_10621246)
- Drosha (D28B1) Rabbit mAb (RRID:AB_2238644)
- Recombinant Anti-DGCR8 antibody [EPR18757] (RRID:AB_2892625)
- Anti-DDX1 (RRID:AB_10795025)
- Argonaute 4 (D10F10) Rabbit mAb (RRID:AB_10828811)
- AGO1-human (RRID:AB_2616013)
- Rabbit Anti-Argonaute 2 Monoclonal Antibody, Unconjugated, Clone C34C6 (RRID:AB_2096291)
- Argonaute 3 (D15D2) Rabbit mAb (RRID:AB_2797607)
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This is a list of tools and resources that we have found mentioned in this publication.
Anti-SF3B3 polyclonal antibody (antibody)
RRID:AB_10960386
This polyclonal targets SF3B3
View all literature mentionsAnti-DDX1 antibody produced in rabbit (antibody)
RRID:AB_10794321
This polyclonal targets DDX1 antibody produced in rabbit
View all literature mentionsAnti-CPSF3 antibody produced in rabbit (antibody)
RRID:AB_10669728
This polyclonal targets CPSF3 antibody produced in rabbit
View all literature mentionsBiotin anti-mouse/human KLRG1 (MAFA) (antibody)
RRID:AB_10578565
This monoclonal targets KLRG1
View all literature mentionsBiotin anti-mouse CD115 (CSF-1R) (antibody)
RRID:AB_2028401
This monoclonal targets CD115
View all literature mentionsBiotin anti-mouse CD103 (antibody)
RRID:AB_535947
This monoclonal targets CD103
View all literature mentionsBiotin anti-mouse CD135 (antibody)
RRID:AB_1953267
This monoclonal targets CD135
View all literature mentionsBiotin anti-mouse CD127 (IL-7Ralpha) (antibody)
RRID:AB_2126118
This monoclonal targets CD127
View all literature mentionsAPC anti-mouse CD93 (AA4.1, early B lineage) (antibody)
RRID:AB_2275879
This monoclonal targets CD93
View all literature mentionsPurified anti-mouse CD117 (c-kit) Recombinant (antibody)
RRID:AB_2734232
This recombinant monoclonal targets CD117
View all literature mentionsAlexa Fluor(R) 488 anti-mouse Ly-6G (antibody)
RRID:AB_2561340
This monoclonal targets Ly-6G
View all literature mentionsAlexa Fluor(R) 488 anti-mouse Ly-6C (antibody)
RRID:AB_10640820
This monoclonal targets Ly-6C
View all literature mentionsBiotin anti-mouse Ly-6A/E (Sca-1) (antibody)
RRID:AB_313340
This monoclonal targets Ly-6A/E
View all literature mentionsPacific Blue anti-mouse Lineage Cocktail (antibody)
RRID:AB_11150779
This monoclonal targets Pacific Blue anti-mouse Lineage Cocktail
View all literature mentionsCD279 (PD-1) Monoclonal Antibody (J43), FITC, eBioscience (antibody)
RRID:AB_465472
This monoclonal targets CD279 (PD-1)
View all literature mentionsIL-13 Monoclonal Antibody (eBio13A), PE, eBioscience (antibody)
RRID:AB_763559
This monoclonal targets IL-13
View all literature mentionsAlexa Fluor(R) 488 anti-mouse IFN-gamma (antibody)
RRID:AB_493312
This monoclonal targets IFN-gamma
View all literature mentionsPurified anti-mouse/human IL-5 (antibody)
RRID:AB_315326
This monoclonal targets IL-5
View all literature mentionsPurified anti-mouse IL-4 (antibody)
RRID:AB_315316
This monoclonal targets IL-4
View all literature mentionsAlexa Fluor(R) 488 anti-mouse I-A/I-E (antibody)
RRID:AB_493523
This monoclonal targets I-A/I-E
View all literature mentionsMs Siglec-F Biotin E50-2440 100ug (antibody)
RRID:AB_2916663
This unknown targets Siglec-F
View all literature mentionsFOXP3 Monoclonal Antibody (FJK-16s), PE, eBioscience (antibody)
RRID:AB_465936
This monoclonal targets FOXP3
View all literature mentionsAPC anti-mouse CD278 (ICOS) (antibody)
RRID:AB_2728129
This monoclonal targets CD278
View all literature mentionsPurified anti-mouse CD86 (antibody)
RRID:AB_313145
This monoclonal targets CD86
View all literature mentionsBiotin anti-mouse CD80 (antibody)
RRID:AB_313125
This monoclonal targets CD80
View all literature mentionsPurified anti-mouse CD64 (FcgammaRI) (antibody)
RRID:AB_10613107
This monoclonal targets CD64
View all literature mentionsBiotin anti-mouse CD63 (antibody)
RRID:AB_2860698
This monoclonal targets CD63
View all literature mentionsPurified anti-mouse CD69 (antibody)
RRID:AB_313105
This monoclonal targets CD69
View all literature mentionsPurified anti-mouse CD62L (antibody)
RRID:AB_313089
This monoclonal targets CD62L
View all literature mentionsBiotin anti-mouse CD49b (pan-NK cells) (antibody)
RRID:AB_313411
This monoclonal targets CD49b
View all literature mentionsAlexa Fluor(R) 488 anti-mouse/human CD45R/B220 (antibody)
RRID:AB_389308
This monoclonal targets CD45R
View all literature mentionsPacific Blue(TM) anti-mouse CD45.2 (antibody)
RRID:AB_492873
This monoclonal targets CD45.2
View all literature mentionsBiotin anti-mouse CD45.1 (antibody)
RRID:AB_313492
This monoclonal targets CD45.1
View all literature mentionsCD45 Monoclonal Antibody (30-F11), eBioscience (antibody)
RRID:AB_467251
This monoclonal targets CD45
View all literature mentionsCD44 Monoclonal Antibody (IM7), PE, eBioscience (antibody)
RRID:AB_465664
This monoclonal targets CD44
View all literature mentionsBiotin anti-mouse CD25 (antibody)
RRID:AB_312853
This monoclonal targets CD25
View all literature mentionsAPC anti-mouse TCR beta chain (antibody)
RRID:AB_313435
This monoclonal targets TCR beta chain
View all literature mentionsCD19 Monoclonal Antibody (eBio1D3 (1D3)), FITC, eBioscience (antibody)
RRID:AB_657666
This monoclonal targets CD19
View all literature mentionsPurified anti-mouse CD16/32 (antibody)
RRID:AB_312801
This monoclonal targets CD16/32
View all literature mentionsPurified anti-mouse CD11c Recombinant (antibody)
RRID:AB_2876575
This recombinant monoclonal targets CD11c
View all literature mentionsBiotin anti-mouse/human CD11b (antibody)
RRID:AB_312786
This monoclonal targets CD11b
View all literature mentionsCD8a Monoclonal Antibody (53-6.7), FITC, eBioscience (antibody)
RRID:AB_464915
This monoclonal targets CD8a
View all literature mentionsCD3 Monoclonal Antibody (17A2), eBioscience (antibody)
RRID:AB_467053
This monoclonal targets CD3
View all literature mentionsPurified anti-mouse CD4 (antibody)
RRID:AB_312708
This monoclonal targets CD4
View all literature mentionsGAPDH (D16H11) XP Rabbit mAb (antibody)
RRID:AB_10622025
This monoclonal targets GAPDH
View all literature mentionsLamin A/C Antibody (antibody)
RRID:AB_2136278
This polyclonal targets Lamin A/C
View all literature mentionsc-Myc (D84C12) Rabbit mAb (Alexa Fluor® 647 Conjugate) (antibody)
RRID:AB_2798334
This monoclonal targets Myc
View all literature mentionsHistone H3 antibody [mAbcam 10799] - ChIP Grade (antibody)
RRID:AB_470239
This monoclonal targets Histone H3 antibody [mAbcam 10799] - ChIP Grade
View all literature mentionsRabbit anti-SF3B5 Antibody, Affinity Purified (antibody)
RRID:AB_2891502
This polyclonal targets SF3B5
View all literature mentionsSF3B1 (D7L5T) Rabbit mAb (antibody)
RRID:AB_2798479
This monoclonal targets SF3B1
View all literature mentionsMouse Anti-Human PHF5A Monoclonal, Unconjugated, Clone 2h7 (antibody)
RRID:AB_2165366
This monoclonal targets Human PHF5A
View all literature mentionsAnti-XPO5 antibody produced in rabbit (antibody)
RRID:AB_1848330
This unknown targets Human XPO5
View all literature mentionsRecombinant Anti-SF3B3 antibody [EPR18440] (antibody)
RRID:AB_2910146
This recombinant monoclonal targets SF3B3
View all literature mentionsHSP90 Antibody (antibody)
RRID:AB_2121214
This polyclonal targets HSP90
View all literature mentionsMouse Anti-GW182 Monoclonal Antibody, Unconjugated, Clone 4B6 (antibody)
RRID:AB_1310295
This monoclonal targets GW182
View all literature mentionsGW182 Polyclonal Antibody (antibody)
RRID:AB_2780472
This unknown targets GW182
View all literature mentionsGW182 antibody (antibody)
RRID:AB_10866284
This polyclonal targets GW182 antibody
View all literature mentionsEDC4/Ge-1 Antibody (antibody)
RRID:AB_10621246
This polyclonal targets EDC4/Ge-1
View all literature mentionsDrosha (D28B1) Rabbit mAb (antibody)
RRID:AB_2238644
This monoclonal targets DROSHA
View all literature mentionsRecombinant Anti-DGCR8 antibody [EPR18757] (antibody)
RRID:AB_2892625
This recombinant monoclonal targets DGCR8
View all literature mentionsArgonaute 4 (D10F10) Rabbit mAb (antibody)
RRID:AB_10828811
This monoclonal targets Argonaute 4 (D10F10) Rabbit mAb
View all literature mentionsRabbit Anti-Argonaute 2 Monoclonal Antibody, Unconjugated, Clone C34C6 (antibody)
RRID:AB_2096291
This monoclonal targets Argonaute 2
View all literature mentionsArgonaute 3 (D15D2) Rabbit mAb (antibody)
RRID:AB_2797607
This monoclonal targets AGO3
View all literature mentionsAgo3tm1a(KOMP)Wtsi (organism)
RRID:IMSR_KOMP:CSD80199
gene symbol note: argonaute RISC catalytic subunit 3 mutant strain targeted mutation 1a, Wellcome Trust Sanger Institute This is a legacy resource.
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsB6.129S2-Tcratm1Mom/J (organism)
RRID:IMSR_JAX:002116
Mus musculus with name B6.129S2-Tcratm1Mom/J from IMSR.
View all literature mentions
