Biosynthesis of 7-Deazaguanosine-Modified tRNA Nucleosides: a New Role for GTP Cyclohydrolase I
Biosynthesis of 7-Deazaguanosine-Modified tRNA Nucleosides: a New Role for GTP Cyclohydrolase I
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DOI：
10.1128/jb.00874-08
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发表时间：
2008-12-01
影响因子：
3.2
通讯作者：
de Crecy-Lagard, Valerie
中科院分区：
文献类型：
--
作者：
Phillips, Gabriella;El Yacoubi, Basma;de Crecy-Lagard, Valerie
古核苷（Q）和古核苷（G（+））是在tRNA中发现的高度修饰的核糖核苷。Q存在于真核生物和细菌中tRNA（GUN）的反密码子区域，而G（+）存在于古细菌tRNA D环的第15位。原核生物通过7-氰基-7-脱氮鸟嘌呤（pre-Q（0））中间体从GTP从头产生这些7-脱氮鸟苷衍生物，但哺乳动物输入从饮食或肠道植物群获得的游离碱--鸟嘌呤。通过将比较基因组分析的结果与遗传学研究的结果相结合，我们表明叶酸途径的第一种酶，GTP环化水解酶I（GCYII-I），在大肠杆菌中由folE编码，也是两种原核生物界中前Q（0）生物合成的第一种酶。事实上，从E. coli Delta folE菌株缺乏Q，并且通过表达来自不同细菌或古细菌来源的GCYH-I编码基因来补充该缺陷。以类似的方式，从携带GCYH-I编码基因缺失的Haloferax volcanii菌株中提取的tRNA仅含有痕量的G（+）。这些结果将tRNA修饰碱基的产生与初级代谢联系起来，并进一步阐明了这些复杂修饰核苷的生物合成途径。
Queuosine (Q) and archaeosine (G(+)) are hypermodified ribonucleosides found in tRNA. Q is present in the anticodon region of tRNA(GUN) in Eukarya and Bacteria, while G(+) is found at position 15 in the D-loop of archaeal tRNA. Prokaryotes produce these 7-deazaguanosine derivatives de novo from GTP through the 7-cyano-7-deazaguanine (pre-Q(0)) intermediate, but mammals import the free base, queuine, obtained from the diet or the intestinal flora. By combining the results of comparative genomic analysis with those of genetic studies, we show that the first enzyme of the folate pathway, GTP cyclohydrolase I (GCYII-I), encoded in Escherichia coli by folE, is also the first enzyme of pre-Q(0) biosynthesis in both prokaryotic kingdoms. Indeed, tRNA extracted from an E. coli Delta folE strain is devoid of Q and the deficiency is complemented by expressing GCYH-I-encoding genes from different bacterial or archaeal origins. In a similar fashion, tRNA extracted from a Haloferax volcanii strain carrying a deletion of the GCYH-I-encoding gene contains only traces of G(+). These results link the production of a tRNA-modified base to primary metabolism and further clarify the biosynthetic pathway for these complex modified nucleosides.