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

Area of Science:

• Immunology
• Molecular Biology
• Gene Regulation

Background:

• T cell activation requires gene expression for effector cell differentiation and proliferation.
• RAM (RNMT-Activating Mini protein) is a cofactor for RNA cap methyltransferase RNMT, upregulated upon T cell activation.
• RNA cap formation is vital for RNA stability, processing, and translation.

Purpose of the Study:

• To investigate the role of RAM in T cell activation and its relationship with RNMT.
• To determine the impact of RAM deletion on RNA cap formation, gene expression, and T cell function.

Main Methods:

• Conditional gene deletion of the Ram gene in naïve T cells.
• Analysis of RNA cap formation, gene expression, protein synthesis, and T cell proliferation.
• Comparison of phenotypes between Ram knockout and Rnmt knockout T cells.

Main Results:

• Ram deletion destabilizes RNMT protein and impairs its upregulation upon T cell activation.
• Significant reduction in activation-induced RNA cap formation and gene expression in Ram-deficient T cells.
• Impaired ribosome biogenesis, protein synthesis, and CD4 T cell proliferation in Ram knockout T cells.

Conclusions:

• RAM is essential for stabilizing RNMT and is required for proper T cell activation, RNA cap formation, and gene expression.
• RAM deletion leads to reduced T cell proliferation and protein synthesis, highlighting its critical role in T cell immunity.
• The findings support RAM's function as a crucial cofactor for RNMT in T cells.