Shigi Naoki
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology Tokyo, Japan.
Front Genet. 2014 Apr 2;5:67. doi: 10.3389/fgene.2014.00067. eCollection 2014.
Sulfur is an essential element for a variety of cellular constituents in all living organisms. In tRNA molecules, there are many sulfur-containing nucleosides, such as the derivatives of 2-thiouridine (s(2)U), 4-thiouridine (s(4)U), 2-thiocytidine (s(2)C), and 2-methylthioadenosine (ms(2)A). Earlier studies established the functions of these modifications for accurate and efficient translation, including proper recognition of the codons in mRNA or stabilization of tRNA structure. In many cases, the biosynthesis of these sulfur modifications starts with cysteine desulfurases, which catalyze the generation of persulfide (an activated form of sulfur) from cysteine. Many sulfur-carrier proteins are responsible for delivering this activated sulfur to each biosynthesis pathway. Finally, specific "modification enzymes" activate target tRNAs and then incorporate sulfur atoms. Intriguingly, the biosynthesis of 2-thiouridine in all domains of life is functionally and evolutionarily related to the ubiquitin-like post-translational modification system of cellular proteins in eukaryotes. This review summarizes the recent characterization of the biosynthesis of sulfur modifications in tRNA and the novel roles of this modification in cellular functions in various model organisms, with a special emphasis on 2-thiouridine derivatives. Each biosynthesis pathway of sulfur-containing molecules is mutually modulated via sulfur trafficking, and 2-thiouridine and codon usage bias have been proposed to control the translation of specific genes.
硫是所有生物中多种细胞成分的必需元素。在转运RNA（tRNA）分子中，存在许多含硫核苷，如2-硫代尿苷（s(2)U）、4-硫代尿苷（s(4)U）、2-硫代胞苷（s(2)C）和2-甲硫基腺苷（ms(2)A）的衍生物。早期研究确定了这些修饰对于准确高效翻译的功能，包括对信使RNA（mRNA）中密码子的正确识别或tRNA结构的稳定。在许多情况下，这些硫修饰的生物合成始于半胱氨酸脱硫酶，其催化从半胱氨酸生成过硫化物（硫的一种活化形式）。许多硫载体蛋白负责将这种活化硫传递到每个生物合成途径。最后，特定的“修饰酶”激活目标tRNA，然后掺入硫原子。有趣的是，在生命的所有领域中，2-硫代尿苷的生物合成在功能和进化上与真核生物中细胞蛋白质的泛素样翻译后修饰系统相关。本综述总结了tRNA中硫修饰生物合成的最新特征以及这种修饰在各种模式生物细胞功能中的新作用，特别强调了2-硫代尿苷衍生物。含硫分子的每条生物合成途径都通过硫转运相互调节，并且有人提出2-硫代尿苷和密码子使用偏好可控制特定基因的翻译。
