title: A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification.
abstract: N(6)-threonylcarbamoyladenosine (t(6)A) is a universally conserved, essential modified nucleoside found in transfer RNAs (tRNAs) responsible for ANN codons in all three domains of life. t(6)A has a crucial role in maintaining decoding accuracy during protein synthesis. The presence of t(6)A in cellular tRNAs has been well documented for more than four decades. However, under conditions optimized for nucleoside preparation, we detected little t(6)A in tRNAs from Escherichia coli. Instead, we identified a new modified base named 'cyclic t(6)A' (ct(6)A), which is a cyclized active ester with an oxazolone ring. An E1-like enzyme, CsdL (renamed as TcdA), which catalyzes ATP-dependent dehydration of t(6)A to form ct(6)A, was also identified. Two yeast homologs of tcdA, YHR003C (TCD1) and YKL027W (TCD2), were required for ct(6)A formation and respiratory cell growth. ct(6)A was involved in promoting decoding efficiency. Structural modeling suggests that ct(6)A recognizes the first adenine base of ANN codon at the ribosomal A site.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, the University of Tokyo, Tokyo, Japan.
authors.forename: Kenjyo
authors.initials: K
authors.lastname: Miyauchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D002384:Catalysis; D003062:Codon; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D010081:Oxazolone / Q000737:chemistry; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D012343:RNA, Transfer / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: D003062:Codon; C547583:CsdL protein, E coli; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D010081:Oxazolone; C003268:N(6)-(N-threonylcarbonyl)adenosine; D000255:Adenosine Triphosphate; D012343:RNA, Transfer; D044764:Ubiquitin-Activating Enzymes; D000241:Adenosine