THE ROLE OF SELENIUM IN CELLULAR METABOLISM

硒在人类的饮食中是必不可少的，并且过量或缺乏 这种元素在很小的范围内对健康有害。的确有 大量证据支持硒在减轻癌症中的作用 和心脏病，以及延缓衰老过程的作用。既然是这样 元素发挥其作用，至少部分作为 蛋白质，我们的目标是了解硒是如何结合到 蛋白。因此，我们正在研究体内捐赠硒的tRNA。 硒半胱氨酸的形式转化为蛋白质。有趣的是，硒半胱氨酸 首次氨基酰化的硒半胱氨酸tRNA生物合成 丝氨酸。在过去的一年里，我们已经表明， 丝氨酸tRNA合成酶的硒半胱氨酸tRNA和丝氨酸tRNA位于 主要是在位置73的鉴别器底座中和在长 两个tRNA的额外手臂。长长的多出的手臂以定向的方式工作-- 丝氨酸tRNA中的长度特异方式，此外，在序列中- 硒半胱氨酸tRNA中的特异方式。这些tRNA的其他结构域 (即，接受者、D和T词干)有助于识别 过程，但不能达到鉴别器基数和长 多一只胳膊。我们还明确地表明，相同的合成酶和 至少有一些相同的识别位点用于氨基酰化反应 两个都是tRNA。此外，我们已经证明，UUA(一种亮氨酸密码子) 或者UAA(一种无意义的密码子)可以用于将硒半胱氨酸插入到 蛋白质，前提是硒半胱氨酸tRNA含有反密码子 与相应密码子互补。这一观察结果非常 重要的是证明了硒半胱氨酸的密码子UGA， 不是硒半胱氨酸插入蛋白质的关键元件。 我们还发现，A盒和B盒是内部的 所有真核tRNA基因表达的控制区不是 参与硒半胱氨酸tRNA基因转录。然而，这些 内部因素在预告片序列的处理中确实起到了作用。

Selenium is essential in the human diet and excesses or deficiencies of this element within a narrow range are detrimental to health. There is substantial evidence supporting a role of selenium in alleviating cancer and heart disease and a role in delaying the aging process. Since this element exerts its effects, at least in part, as a constituent of protein, our goal is to understand how selenium is incorporated into protein. Thus, we are examining the tRNAs that donate selenium in the form of selenocysteine to protein. Interestingly, selenocysteine is biosynthesized on selenocysteine tRNA which is first aminoacylated with serine. In the past year, we have shown that the identity elements in selenocysteine tRNA and serine tRNA for seryl-tRNA synthetase are located principally in the discriminator base at position 73 and in the long extra arm of both tRNAs. The long extra arm acts in an orientation- and length-specific manner in serine tRNA, and in addition, in a sequence- specific manner in selenocysteine tRNA. The other domains of these tRNAs (i.e., the acceptor, D and T stems) contribute to the recognition process, but not to the extent of the discriminator base and the long extra arm. We have also shown unequivocally that the same synthetase and at least some of the same recognition sites are used in aminoacylating both tRNAs. In addition, we have shown that either UUA (a leucine codon) or UAA (a nonsense codon) can serve for inserting selenocysteine into protein provided the selenocysteine tRNA contains an anticodon complementary to the corresponding codon. This observation very importantly demonstrates that UGA, which is the codon for selenocysteine, is not the critical element for selenocysteine insertion into protein. We have also found that the A box and B box, which are the internal control regions for expression of all eukaryotic tRNA genes, are not involved in selenocysteine tRNA gene transcription. However, these internal elements do play a role in processing of the trailer sequence.