Journal article

Severe Impairment of TNF Post-transcriptional Regulation Leads to Embryonic Death

Elise Clayer, Destiny Dalseno, Andrew Kueh, Derek Lacey, Minhsuang Tsai, Elysa Carr, Verena C Wimmer, Philippe Bouillet

iScience | CELL PRESS | Published : 2020


Post-transcriptional regulation mechanisms control mRNA stability or translational efficiency via ribosomes, and recent evidence indicates that it is a major determinant of the accurate levels of cytokine mRNAs. Transcriptional regulation of Tnf has been well studied and found to be important for the rapid induction of Tnf mRNA and regulation of the acute phase of inflammation, whereas study of its post-transcriptional regulation has been largely limited to the role of the AU-rich element (ARE), and to a lesser extent, to that of the constitutive decay element (CDE). We have identified another regulatory element (NRE) in the 3' UTR of Tnf and demonstrate that ARE, CDE, and NRE cooperate in v..

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Awarded by Australian NHMRC

Awarded by Leukemia and Lymphoma Society (Specialised Center of Research)

Funding Acknowledgements

We thank J. Stanley, T. Kitson. M. Watters, and G. Siciliano for animal care and expertise; J. Corbin, K. Weston, and T. Nikolaou for automated blood analysis; T. Mak (The Campbell Family Institute for Breast Cancer Research) for TNFR1 KOmice; and J. Silke for TNF KO mice. This work was supported by the Australian NHMRC (Program Grant 461221, Research Fellowship 1042629, Project grant 1127885), the Leukemia and Lymphoma Society (Specialised Center of Research grant 7015), the Arthritis Australia Zimmer fellowship, and infrastructure support from the NHMRC (IRISS), and the Victorian State Government (OIS). The generation of TNFdel4, TNFdel5, TNFdel6, TNFdel4del5, and TNFdel4del6 mice used in this study was supported by the Australian Phenomics Network (APN) and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program.