S-Adenosyl Homocysteine Hydrolase Is Required for Myc-Induced mRNA Cap Methylation, Protein Synthesis, and Cell Proliferation. / Fernandez-Sanchez, Maria Elena; Gonatopoulos-Pournatzis, Thomas; Preston, Gavin; Lawlor, Margaret A.; Cowling, Victoria H.
In: Molecular and Cellular Biology, Vol. 29, No. 23, 01.12.2009, p. 6182-6191.Research output: Contribution to journal › Article
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TY - JOUR
T1 - S-Adenosyl Homocysteine Hydrolase Is Required for Myc-Induced mRNA Cap Methylation, Protein Synthesis, and Cell Proliferation
A1 - Fernandez-Sanchez,Maria Elena
A1 - Gonatopoulos-Pournatzis,Thomas
A1 - Preston,Gavin
A1 - Lawlor,Margaret A.
A1 - Cowling,Victoria H.
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 - <p>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.</p>
AB - <p>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.</p>
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
U2 - 10.1128/MCB.00973-09
DO - 10.1128/MCB.00973-09
M1 - Article
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 23
VL - 29
SP - 6182
EP - 6191
ER -