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.
Skip Nav Destination
Article navigation
May 2005
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
May 10 2005
Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5)
Stéphane RICHARD;
Stéphane RICHARD
1
1Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology and Medicine, McGill University, Montréal, Québec, Canada H3T 1E2
1To whom correspondence should be addressed, at Lady Davis Institute for Medical Research, 3755 Côte Ste-Catherine Road, Montréal, Québec, Canada H3T 1E2 (email stephane.richard@mcgill.ca).
Search for other works by this author on:
Mélanie MOREL;
Mélanie MOREL
1Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology and Medicine, McGill University, Montréal, Québec, Canada H3T 1E2
Search for other works by this author on:
Patrick CLÉROUX
Patrick CLÉROUX
1Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology and Medicine, McGill University, Montréal, Québec, Canada H3T 1E2
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 08 2004
Revision Received:
January 10 2005
Accepted:
January 18 2005
Accepted Manuscript online:
January 18 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 388 (1): 379–386.
Article history
Received:
March 08 2004
Revision Received:
January 10 2005
Accepted:
January 18 2005
Accepted Manuscript online:
January 18 2005
Citation
Stéphane RICHARD, Mélanie MOREL, Patrick CLÉROUX; Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5). Biochem J 15 May 2005; 388 (1): 379–386. doi: https://doi.org/10.1042/BJ20040373
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.