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Molecular and Cellular Biology, December 2009, p. 6182-6191, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00973-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

S-Adenosyl Homocysteine Hydrolase Is Required for Myc-Induced mRNA Cap Methylation, Protein Synthesis, and Cell Proliferation {triangledown}

Maria Elena Fernandez-Sanchez,1 Thomas Gonatopoulos-Pournatzis,1 Gavin Preston,1 Margaret A. Lawlor,2 and Victoria H. Cowling1*

Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom,1 Axis-Shield Diagnostics Ltd., Luna Place, The Technology Park, Dundee DD2 1XA, United Kingdom2

Received 23 July 2009/ Returned for modification 1 September 2009/ Accepted 23 September 2009

The c-Myc proto-oncogene promotes mRNA cap methylation, which is essential for almost all mRNA translation. The mRNA cap methylation reaction produces an inhibitory byproduct, S-adenosyl homocysteine. Here we report that Myc promotes upregulation of S-adenosyl homocysteine hydrolase (SAHH), an enzyme which hydrolyzes S-adenosyl homocysteine, thus neutralizing its inhibitory effects, and this is required for c-Myc-induced mRNA cap methylation. c-Myc-induced mRNA cap methylation was repressed by inhibiting the expression or activity of SAHH, whereas the same treatments did not have a significant effect on c-Myc-induced transcription or other c-Myc-dependent methylation events. The selective inhibition of mRNA cap methylation afforded by SAHH repression revealed that c-Myc-induced cap methylation could be correlated with the core c-Myc functions of protein synthesis, cell proliferation, and cell transformation.

* Corresponding author. Mailing address: Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom. Phone: 44(0)1382 386997. Fax: 44(0)1382 385783. E-mail: v.h.cowling{at}dundee.ac.uk

{triangledown} Published ahead of print on 5 October 2009.

Molecular and Cellular Biology, December 2009, p. 6182-6191, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00973-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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