|
| Status |
Public on Oct 31, 2024 |
| Title |
Argonaute3-SF3B3 complex controls pre-mRNA splicing to restrain Type-2 immunity [RNA-seq: dissected tissues] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Argonaute (AGO) proteins execute Micro-RNA (miRNA) mediated gene silencing. However it is currently debated whether all 4 mammalian AGO proteins (AGO1, AGO2, AGO3 and AGO4) are required for miRNA activity. To address this, we generated a mouse with deleted Ago1, Ago3 and Ago4 genes (Ago134), and found that these Argonaute proteins are completely redundant for miRNA biogenesis, miRNA homeostasis or miRNA function, a role that is carried out exclusively by AGO2. Instead, AGO1/3/4 are required to curtail the expansion of Type-2 adaptive immunity in mice via regulation of precursor-mRNA (pre-mRNA) splicing in CD4+ 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. Our work uncouples AGO1, AGO3 and AGO4 from miRNA-mediated RNAi, discovers a new AGO3:SF3B3 complex in the cellular nucleus, and reveals an underappreciated mechanism by which AGO proteins prevent hyper-inflammatory disease.
|
| |
|
| Overall design |
Comparison of gene expression from tissues isolated from either wild-type or AGO1/AGO3/AGO4 knockout mice.
|
| |
|
| Contributor(s) |
Guidi R, Hackney J, Wedeles C, Guillory J, Modrusan Z |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 26, 2023 |
| Last update date |
Oct 31, 2024 |
| Contact name |
Jason A Hackney |
| E-mail(s) |
[email protected]
|
| Organization name |
Genentech, Inc.
|
| Department |
Department of Bioinformatics and Computational Biology
|
| Street address |
1 DNA Way
|
| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (78)
|
|
| This SubSeries is part of SuperSeries: |
| GSE243918 |
Argonaute3-SF3B3 complex controls pre-mRNA splicing to restrain Type-2 immunity |
|
| Relations |
| BioProject |
PRJNA1021190 |
Less...
More...