N. Radomski et al., Nuclear accumulation of S-adenosylhomocysteine hydrolase in transcriptionally active cells during development of Xenopus laevis, MOL BIOL CE, 10(12), 1999, pp. 4283-4298
The oocyte nuclear antigen of the monoclonal antibody 32-5B6 of Xenopus lae
vis is subject to regulated nuclear translocation during embryogenesis. It
is distributed in the cytoplasm during oocyte maturation, where it remains
during cleavage and: blastula stages, before it gradually reaccumulates in
the nuclei during gastrulation, We have now identified this antigen to be t
he enzyme S-adenosylhomocysteine hydrolase (SAHH). SAHH is the only enzyme
that cleaves S-adenosylhomocysteine, a reaction product and an inhibitor of
all S-adenosylmethionine-dependent methylation reactions. We have compared
the spatial and temporal patterns of nuclear localization of SAHH and of n
uclear methyltransferase activities during embryogenesis and in tissue cult
ure cells. Nuclear localization of Xenopus SAHH did not temporally correlat
e with DNA methylation. However, we found that SAHH nuclear localization co
incides with high rates of mRNA synthesis, a subpopulation colocalizes With
RNA polymerase II, and inhibitors of SAHH reduce both methylation and synt
hesis of poly(A)(+) RNA. We therefore propose that accumulation of SAHH in
the nucleus may be required for efficient cap methylation in transcriptiona
lly active cells. Mutation analysis revealed that the C terminus and the N
terminus are both required for efficient nuclear translocation in tissue cu
lture cells, indicating that more than one interacting domain contributes t
o nuclear accumulation of Xenopus SAHH.