Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
EMBO J. 2011 Mar 2;30(5):882-93. doi: 10.1038/emboj.2010.363. Epub 2011 Feb 1.
The YgjD/Kae1 family (COG0533) has been on the top-10 list of universally conserved proteins of unknown function for over 5 years. It has been linked to DNA maintenance in bacteria and mitochondria and transcription regulation and telomere homeostasis in eukaryotes, but its actual function has never been found. Based on a comparative genomic and structural analysis, we predicted this family was involved in the biosynthesis of N(6)-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs decoding ANN codons. This was confirmed as a yeast mutant lacking Kae1 is devoid of t(6)A. t(6)A(-) strains were also used to reveal that t(6)A has a critical role in initiation codon restriction to AUG and in restricting frameshifting at tandem ANN codons. We also showed that YaeZ, a YgjD paralog, is required for YgjD function in vivo in bacteria. This work lays the foundation for understanding the pleiotropic role of this universal protein family.
YgjD/Kae1 家族（COG0533）在未知功能的普遍保守蛋白的前 10 名列表中已经超过 5 年了。它与细菌和线粒体中的 DNA 维持以及真核生物中的转录调控和端粒稳态有关，但它的实际功能从未被发现。基于比较基因组学和结构分析，我们预测这个家族参与 N(6)-threonylcarbamoyl adenosine 的生物合成，这是一种在解码 ANN 密码子的 tRNA 位置 37 处发现的普遍修饰。这一点得到了证实，因为缺乏 Kae1 的酵母突变体缺乏 t(6)A。t(6)A(-)菌株也被用于揭示 t(6)A 在起始密码子限制为 AUG 和限制串联 ANN 密码子的移码方面起着关键作用。我们还表明，YaeZ，YgjD 的 paralog，在细菌体内 YgjD 的功能中是必需的。这项工作为理解这个普遍的蛋白质家族的多效性作用奠定了基础。
