TY - JOUR
T1 - S-Adenosyl Homocysteine Hydrolase Is Required for Myc-Induced mRNA Cap Methylation, Protein Synthesis, and Cell Proliferation
AU - Fernandez-Sanchez, Maria Elena
AU - Gonatopoulos-Pournatzis, Thomas
AU - Preston, Gavin
AU - Lawlor, Margaret A.
AU - Cowling, Victoria H.
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
KW - CARBOXY-TERMINAL DOMAIN
KW - POLYMERASE-II
KW - CAPPING ENZYME
KW - C-MYC
KW - ADENOSYLHOMOCYSTEINE HYDROLASE
KW - GENOMIC TARGETS
KW - XENOPUS-LAEVIS
KW - TRANSCRIPTION
KW - METHYLTRANSFERASE
KW - TRANSLATION
UR - http://www.scopus.com/inward/record.url?scp=71949113286&partnerID=8YFLogxK
U2 - 10.1128/MCB.00973-09
DO - 10.1128/MCB.00973-09
M3 - Article
C2 - 19805518
VL - 29
SP - 6182
EP - 6191
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 23
ER -