Abstract
The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-kappa B signaling. The roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3-deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell-specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased IFN signaling, which increased the proportion of immature B and innate immune cells, and suppressed follicle and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Unlike Regnase-1, Regnase-3 expression is high specifically in macrophages and is transcriptionally controlled by IFN signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade, and regulate mRNAs, such as Zc3h12a (Regnase-1), in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin
Mathematik, Informatik und Statistik > Informatik Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
000 Informatik, Informationswissenschaft, allgemeine Werke > 004 Informatik |
| URN: | urn:nbn:de:bvb:19-epub-78305-0 |
| ISSN: | 0022-1007 |
| Sprache: | Englisch |
| Dokumenten ID: | 78305 |
| Datum der Veröffentlichung auf Open Access LMU: | 15. Dez. 2021, 14:43 |
| Letzte Änderungen: | 13. Aug. 2024, 12:59 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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