Abstract
Arginine methylation is a post-translational modification resulting in the generation of aDMAs (asymmetrical ω-NG, NG-dimethylated arginines) and sDMAs (symmetrical ω-NG, N′G-dimethylated arginines). The role of arginine methylation in cell signalling and gene expression in T lymphocytes is not understood. In the present study, we report a role for protein arginine methylation in regulating IL-2 (interleukin 2) gene expression in T lymphocytes. Leukaemic Jurkat T-cells treated with a known methylase inhibitor, 5′-methylthioadenosine, had decreased cytokine gene expression, as measured using an NF-AT (nuclear factor of activated T-cells)-responsive promoter linked to the luciferase reporter gene. Since methylase inhibitors block all methylation events, we performed RNA interference with small interfering RNAs against the major PRMT (protein arginine methyltransferases) that generates sDMA (PRMT5). The dose-dependent decrease in PRMT5 expression resulted in the inhibition of both IL-2- and NF-AT-driven promoter activities and IL-2 secretion. By using an sDMA-specific antibody, we observed that sDMA-containing proteins are directly associated with the IL-2 promoter after T-cell activation. Since changes in protein arginine methylation were not observed after T-cell activation in Jurkat and human peripheral blood lymphocytes, our results demonstrate that it is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression.
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Dates
Type | When |
---|---|
Created | 20 years, 3 months ago (May 10, 2005, 12:27 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 22, 2021, 9:08 a.m.) |
Indexed | 2 weeks, 4 days ago (Aug. 19, 2025, 6:48 a.m.) |
Issued | 20 years, 3 months ago (May 10, 2005) |
Published | 20 years, 3 months ago (May 10, 2005) |
Published Online | 20 years, 3 months ago (May 10, 2005) |
Published Print | 20 years, 3 months ago (May 15, 2005) |
@article{RICHARD_2005, title={Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5)}, volume={388}, ISSN={1470-8728}, url={http://dx.doi.org/10.1042/bj20040373}, DOI={10.1042/bj20040373}, number={1}, journal={Biochemical Journal}, publisher={Portland Press Ltd.}, author={RICHARD, Stéphane and MOREL, Mélanie and CLÉROUX, Patrick}, year={2005}, month=may, pages={379–386} }