RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression

Knop, K., Gomez-Moreira, C., Galloway, A., Ditsova, D. and Cowling, V. H. (2023) RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression. Discovery Immunology, (doi: 10.1093/discim/kyad021) (Early Online Publication)

Abstract

On T cell activation, upregulation of gene expression produces the protein required for the differentiation and proliferation of effector cell populations. RAM, the co-factor of the RNA cap methyltransferase RNMT, is upregulated following activation. Formation of the RNA cap protects RNA during synthesis and guides RNA processing and translation. Using conditional gene deletion, we found that Ram expression stabilises RNMT protein in T cells and is required for its upregulation on activation. When the Ram gene is deleted in naïve T cells, there are major impacts on activation-induced RNA cap formation and gene expression. Activated T cell proliferation is dependent on increased ribosome production; in Ram knock-out T cells activation-induced expression of ribosomal protein genes and snoRNAs is most severely reduced. Consistent with these changes, Ram deletion resulted in reduced protein synthesis, and reduced growth and proliferation of CD4 T cells. Deletion of Ram results in a similar but milder phenotype to Rnmt deletion, supporting the role of RAM as a RNMT co-factor.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK core funding to the CRUK Beatson Institute (A31287), by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [769080]; a Wellcome Trust Investigator Award (219416/Z/19/Z) to V.H.C, and a Royal Society Wolfson Research Merit Award [WRM\R1\180008].
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cowling, Professor Victoria
• Authors: Knop, K., Gomez-Moreira, C., Galloway, A., Ditsova, D., and Cowling, V. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Discovery Immunology
• Publisher: Oxford University Press
• ISSN: 2754-2483
• ISSN (Online): 2754-2483
• Published Online: 17 November 2023
• Copyright Holders: Copyright: © The Author(s) 2023
• First Published: First published in Discovery Immunology 2023
• Publisher Policy: Reproduced under a Creative Commons licence