Biogenesis and functions of aminocarboxypropyluridine in tRNA

• Published in: Nature communications 2019-12, Vol.10 (1), p.5542-12, Article 5542
• Main Authors: Takakura, Mayuko, Ishiguro, Kensuke, Akichika, Shinichiro, Miyauchi, Kenjyo, Suzuki, Tsutomu
• Format: Article
• Language: English
• Subjects: 38/90; 45/41; 631/337/1645/2570; 631/337/574/1793; 82/1; 82/29; 82/51; 82/58; 82/80; Adenosylmethionine; Biosynthesis; D-loops; E coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Genomic instability; Growth rate; Heat stress; Heat tolerance; Homology; Humanities and Social Sciences; Models, Molecular; Molecular Structure; multidisciplinary; Nucleic Acid Conformation; Post-transcription; RNA, Bacterial - chemistry; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; RNA, Transfer - chemistry; RNA, Transfer - genetics; RNA, Transfer - metabolism; S-Adenosylmethionine; Science; Science (multidisciplinary); Thermal stability; tRNA; Uridine; Uridine - chemistry; Uridine - genetics; Uridine - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13525-3

Transfer (t)RNAs contain a wide variety of post-transcriptional modifications, which play critical roles in tRNA stability and functions. 3-(3-amino-3-carboxypropyl)uridine (acp 3 U) is a highly conserved modification found in variable- and D-loops of tRNAs. Biogenesis and functions of acp 3 U have not been extensively investigated. Using a reverse-genetic approach supported by comparative genomics, we find here that the Escherichia coli yfiP gene, which we rename tapT (tRNA aminocarboxypropyltransferase), is responsible for acp 3 U formation in tRNA. Recombinant TapT synthesizes acp 3 U at position 47 of tRNAs in the presence of S -adenosylmethionine. Biochemical experiments reveal that acp 3 U47 confers thermal stability on tRNA. Curiously, the Δ tapT strain exhibits genome instability under continuous heat stress. We also find that the human homologs of tapT , DTWD1 and DTWD2 , are responsible for acp 3 U formation at positions 20 and 20a of tRNAs, respectively. Double knockout cells of DTWD1 and DTWD2 exhibit growth retardation, indicating that acp 3 U is physiologically important in mammals. E. coli and human tRNAs contain 3-(3-amino-3-carboxypropyl)uridine (acp 3 U) modification. Here the authors identify E. coli TapT and human DTWD1/2 as tRNA aminocarboxypropyltransferases responsible for acp 3 U formation. Inhibition of acp 3 U modification results in genome instability in heat-stressed E. coli and growth defects in human cells.