Aminocarboxypropyl (acp) modified nucleotides in RNA: enzymes, structures and functions

RNA 中氨基羧丙基 (acp) 修饰的核苷酸：酶、结构和功能

• 批准号: 404989355
• 负责人: Professor Dr. Karl-Dieter Entian
• 金额: --
• 依托单位: Institut für Molekulare Biowissenschaften
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404989355?language=en
• 关键词: Aminocarboxypropyl; acp; modified; nucleotides; RNA

The m1acp3Ѱ1191 (S. cerevisiae) hypermodification is unique and presumably present in the 18S rRNAs of all eukaryotes. During the first period of the SPP we functionally and structurally characterized Tsr3 - the enzyme transferring an acp group to m1Ѱ during the last step in the biosynthesis of this hypermodified nucleotide. We solved X-ray structures of archaeal homologs of Tsr3 in the SAM-bound and the apo state. Surprisingly, Tsr3 showed the same fold similar as SPOUT-class RNA methyltransferases but a unique SAM-binding mode that supports the transfer of the acp group of SAM to its RNA substrate. A DTW sequence motive is an integral structural part of this SAM-binding site. These structural insights and sequence similarities opened a new access for the identification of acp transferases. Proteins with predicted DTW motives are widespread in all domains of life. For E. coli our current data suggest that the DTW protein YfiP catalyzes the acp3U-47 modification in tRNAs but is only efficient when an m7G-46 modification is also present. Furthermore, in higher eukaryotes several homologs of tRNA acp transferases are present, some of which possibly modify specifically tRNAs from different organelles. The functional importance of acp modification for tRNAs will be investigated. We also will delineate the structural basis for tRNA recognition of this enzyme class and compare it with the probably different binding mode of Tsr3 proteins to their ribosomal RNA substrates.

M1acp3ѱ1191（S。cerevisie）在所有真核生物的18S rRNA中是独一无二的，我们在所有功能和结构上都表征了TSR3 - 在这项超级核能的生物合成中，将ACP组传递到M1ѱ - Gly的射线结构。识别ACP转移酶的蛋白质具有预测的DTW动机。同样存在。