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Alterations in cell tetrahydrobiopterin levels may regulate queuine hypomodification of tRNA during differentiation of murine erythroleukemia cells.

Abstract：

:The base at the first anticodon ("wobble") position of certain eukaryotic tRNA species is either guanine or the hypermodified base queuine. These tRNA species are synthesized with guanine in the wobble position (tRNAG); this guanine can then be replaced with queuine by the action of the enzyme tRNA-guanine ribosyltransferase. In the present report, we show that tRNAG levels increased in response to the induction of erythroid differentiation of murine erythroleukemia (MEL) cells. We also found that tRNA-guanine ribosyltransferase was significantly inhibited by tetrahydrobiopterin. MEL cells showed a transient threefold increase in tetrahydrobiopterin levels 6 to 12 h after exposure of the cells to inducers such as DMSO or tetramethylurea. The increase in tetrahydrobiopterin preceded the increase in tRNAG which in turn preceded the appearance of phenotypic changes characteristic of differentiation. By contrast, a mutant MEL cell line unable to differentiate in response to inducers showed no change in the level of tetrahydrobiopterin or of tRNAG upon exposure to DMSO. N-acetylserotonin, a well-characterized inhibitor of tetrahydrobiopterin synthesis, prevented the DMSO-mediated increase in tetrahydrobiopterin in normal MEL cells. N-acetylserotonin also inhibited the increase in tRNAG levels and the appearance of phenotypic differentiation in these cells.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Parniak MA,Andrejchyshyn S,Marx S,Kleiman L

doi

10.1016/0014-4827(91)90506-p

subject

Has Abstract

pub_date

1991-07-01 00:00:00

pages

114-8

issue

1

eissn

0014-4827

issn

1090-2422

pii

0014-4827(91)90506-P

journal_volume

195

pub_type

杂志文章

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