Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis. (November 2018)

• Record Type: Journal Article
• Authors: Taniguchi, Takaaki; Miyauchi, Kenjyo; Sakaguchi, Yuriko; Yamashita, Seisuke; Soma, Akiko; Tomita, Kozo; Suzuki, Tsutomu
• Is Part Of: Nature chemical biology. Volume 14:Number 11(2018)
• Page Start: 1010
• Page End: 1020
• Publication Date: 2018-11
• Subjects: Biochemistry -- Periodicals; Biochimie -- Périodiques; 572.05
• DOI: 10.1038/s41589-018-0119-z
• Languages: English
• ISSNs: 1552-4450

Abstract

Abstract Modification of tRNA anticodons plays a critical role in ensuring accurate translation.N 4 -acetylcytidine (ac4 C) is present at the anticodon first position (position 34) of bacterial elongator tRNAMet . Herein, we identifiedBacillus subtilis ylbM (renamedtmcAL ) as a novel gene responsible for ac4 C34 formation. Unlike general acetyltransferases that use acetyl-CoA, TmcAL activates an acetate ion to form acetyladenylate and then catalyzes ac4 C34 formation through a mechanism similar to tRNA aminoacylation. The crystal structure of TmcAL with an ATP analog reveals the molecular basis of ac4 C34 formation. The ΔtmcAL strain displayed a cold-sensitive phenotype and a strong genetic interaction withtilS that encodes the enzyme responsible for synthesizing lysidine (L) at position 34 of tRNAIle to facilitate AUA decoding. Mistranslation of the AUA codon as Met in the ΔtmcAL strain upontilS repression suggests that ac4 C34 modification of tRNAMet and L34 modification of tRNAIle act cooperatively to prevent misdecoding of the AUA codon. A comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein synthesis.