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.
Item Type: | Journal article |
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Faculties: | Medicine Mathematics, Computer Science and Statistics > Computer Science Medicine > Munich Cluster for Systems Neurology (SyNergy) |
Subjects: | 600 Technology > 610 Medicine and health 000 Computer science, information and general works > 004 Data processing computer science |
URN: | urn:nbn:de:bvb:19-epub-78305-0 |
ISSN: | 0022-1007 |
Language: | English |
Item ID: | 78305 |
Date Deposited: | 15. Dec 2021, 14:43 |
Last Modified: | 13. Aug 2024, 12:59 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |