A cyclic form of N 6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification

摘要

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.