Mizutani Takaharu, Osaka Takashi, Ito Yuko, Kanou Masanobu, Usui Toru, Sone Yumiko, Totsuka Tsuyoshi
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603 Japan.
Mol Biol Rep. 2002 Sep;29(3):293-300. doi: 10.1023/a:1020423705963.
One of the Ser-tRNAs, Ser-tRNA(Sec), is converted to Sec-tRNA(Sec) by Sec synthase. This Ser-tRNA(Sec) is also converted to phosphoser-tRNA(Sec) by tRNA kinase. In this study, we analyzed of the products of phosphorylation with tRNA kinase. [3H]Ser-tRNA(Sec) purified on Sephacryl S-200 was phosphorylated with [gamma-32P]ATP by tRNA kinase. The product [32P][3H]phosphoser-tRNA was purified on Sephacryl S-200 and hydrolyzed with ribonuclease T2. The chromatogram of this hydrolyzate on DEAE-cellulose in 7 M urea buffer showed four peaks. The first peak of the pass-through fraction was seryl-adenosine liberated from the 3'-terminal of the tRNA. The second peak, eluted before the third peak containing inorganic phosphate, was phosphoseryl-adenosine. The major compound in the fourth peak was pGp. As a control experiment, non-acylated tRNA(Sec) was used as a substrate of phosphorylation and the product was analyzed. The chromatogram of the digest with ribonuclease T2 showed no peak of phosphoseryl-adenosine, but a peak of pGp was seen with the peak of inorganic phosphate. Thus, the major product in the presence of tRNA kinase was pGp, and a small but significant proportion of the radioactivity was found as phosphoserine in the presence of seryl residue on the 3'-CCA terminal of tRNA(Sec). These results indicated that tRNA kinase phosphorylates not only Ser-tRNA to phosphoser-tRNA but also Gp of the 5'-termini of tRNA to pGp. This study gives a new role to mammalian tRNA kinase.
一种丝氨酸转运RNA(Ser-tRNA),即丝氨酸转运RNA(Sec),可被硒代半胱氨酸合成酶转化为硒代半胱氨酸转运RNA(Sec-tRNA)。这种丝氨酸转运RNA(Sec)也可被tRNA激酶转化为磷酸丝氨酸转运RNA(phosphoser-tRNA)。在本研究中,我们分析了tRNA激酶的磷酸化产物。在Sephacryl S-200上纯化的[3H]丝氨酸转运RNA(Sec)被tRNA激酶用[γ-32P]ATP磷酸化。产物[32P][3H]磷酸丝氨酸转运RNA在Sephacryl S-200上纯化,并用核糖核酸酶T2水解。该水解产物在7M尿素缓冲液中的DEAE-纤维素上的色谱图显示有四个峰。穿透部分的第一个峰是从tRNA的3'-末端释放的丝氨酰腺苷。第二个峰在含有无机磷酸盐的第三个峰之前洗脱,是磷酸丝氨酰腺苷。第四个峰中的主要化合物是pGp。作为对照实验,未酰化的tRNA(Sec)用作磷酸化底物并分析产物。核糖核酸酶T2消化产物的色谱图未显示磷酸丝氨酰腺苷峰,但在无机磷酸盐峰处可见pGp峰。因此,在tRNA激酶存在下的主要产物是pGp,并且在丝氨酸转运RNA(Sec)的3'-CCA末端存在丝氨酰残基的情况下,发现一小部分但显著比例的放射性为磷酸丝氨酸。这些结果表明,tRNA激酶不仅将丝氨酸转运RNA磷酸化为磷酸丝氨酸转运RNA,还将tRNA 5'-末端的Gp磷酸化为pGp。本研究赋予了哺乳动物tRNA激酶一个新的作用。