RNPS1 inhibits excessive tumor necrosis factor/tumor necrosis factor receptor signaling to support hematopoiesis in mice

Journal Article

Significance Messenger RNA (mRNA) splicing is fundamental to protein expression in mammals. Homozygous deletion of single protein components of the splicing machinery or its regulatory factors is embryonic lethal. However, through forward genetic screening in mice, we identified a viable hypomorphic missense mutation of the splicing regulator RNPS1. Homozygous mutant mice displayed altered immune cell development due to excessive tumor necrosis factor (TNF)–dependent immune cell apoptosis. Splicing was impaired in CD8 + T cells and hematopoietic stem cells from RNPS1 mutant mice. TNF knockout rescued hematopoiesis and dramatically reduced splicing defects in RNPS1 hematopoietic cells, demonstrating a surprising link between elevated TNF and defects in splicing caused by RNPS1 deficiency.

Full Text

Duke Authors

Cited Authors

  • Zhong, X; Choi, JH; Hildebrand, S; Ludwig, S; Wang, J; Nair-Gill, E; Liao, T-C; Moresco, JJ; Liu, A; Quan, J; Sun, Q; Zhang, D; Zhan, X; Choi, M; Li, X; Wang, J; Gallagher, T; Moresco, EMY; Beutler, B

Published Date

  • May 3, 2022

Published In

Volume / Issue

  • 119 / 18

Published By

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.2200128119

Language

  • en