Editors' ChoiceRNA Stability

Posttranscriptional Regulation by Methylation?

STKE  26 Nov 2002:
Vol. 2002, Issue 160, pp. tw442-TW442
DOI: 10.1126/stke.2002.160.tw442

The coactivator-associated arginine methyltransferase CARM1 methylates histone H3 and the coactivator p300/CBP to regulate transcription. Li et al. present results that suggest that CARM1 may also regulate RNA stabilization. The mammalian Hu protein HuR is an RNA-binding protein that stabilizes particular mRNAs in response to extracellular signals such as ultraviolet (UV) light, cytokines, or lipopolysaccharide (LPS). However, it is not known how HuR-induced stabilization of mRNAs is actually controlled. Li et al. found that CARM1 can methylate HuR on arginine residues in vitro. They used antibodies to methylated HuR to show that HuR was also methylated in transfected COS-7 cells expressing tagged CARM1 and HuR molecules. Methylation of HuR was enhanced in murine macrophage-like RAW 264.7 cells exposed to LPS. This methylation of HuR correlated with its stabilization of tumor necrosis factor-α mRNA in response to LPS. The authors propose that such methylation may influence nuclear export of HuR or, in some other way, may enhance the protective effects of HuR. It remains to be determined whether methylation is a dynamic signal that can be reversed catalytically or whether the effects of protein methylation can only be removed by sequestration or degradation of the methylated protein.

H. Li, S. Park, B. Kilburn, M. A. Jelinek, A. Henschen-Edman, D. W. Aswad, M. R. Stallcup, I. A. Laird-Offringa, Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. J. Biol. Chem. 277, 44623-44630 (2002). [Abstract] [Full Text]