Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis

Nature Chemical Biology
Takaaki TaniguchiTsutomu Suzuki

Abstract

Modification of tRNA anticodons plays a critical role in ensuring accurate translation. N4-acetylcytidine (ac4C) is present at the anticodon first position (position 34) of bacterial elongator tRNAMet. Herein, we identified Bacillus subtilis ylbM (renamed tmcAL) as a novel gene responsible for ac4C34 formation. Unlike general acetyltransferases that use acetyl-CoA, TmcAL activates an acetate ion to form acetyladenylate and then catalyzes ac4C34 formation through a mechanism similar to tRNA aminoacylation. The crystal structure of TmcAL with an ATP analog reveals the molecular basis of ac4C34 formation. The ΔtmcAL strain displayed a cold-sensitive phenotype and a strong genetic interaction with tilS 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 upon tilS repression suggests that ac4C34 modification of tRNAMet and L34 modification of tRNAIle act cooperatively to prevent misdecoding of the AUA codon.

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Citations

Jul 10, 2019·Nucleic Acids Research·Saori ShinodaTsutomu Suzuki
Sep 17, 2020·Critical Reviews in Biochemistry and Molecular Biology·Federica AccorneroJuan D Alfonzo
Oct 2, 2020·Biopolymers·Kyung W Seo, Ralph E Kleiner
Jan 12, 2019·Cell Research·P Cody He, Chuan He
Aug 30, 2020·Nature Communications·Takeo SuzukiTsutomu Suzuki
Aug 2, 2019·Scientific Reports·Wanqing ZhaoYuan Zhou
Jul 28, 2020·Biomolecules·Ken AsadaRyuji Hamamoto
Jan 23, 2020·Scientific Reports·Rūta StanislauskienėRolandas Meškys
Dec 5, 2020·Current Protocols in Chemical Biology·Keri M BrysonJordan L Meier
Jan 18, 2021·Briefings in Functional Genomics·Satoshi Kimura
Jul 15, 2020·Current Opinion in Microbiology·Satoshi KimuraMatthew K Waldor
Jul 29, 2020·Trends in Microbiology·Valérie de Crécy-Lagard, Marshall Jaroch

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Methods Mentioned

BETA
aminoacylation
size-exclusion chromatography
acetylation
PCR
protein assay
electrophoresis
dot-blot

Software Mentioned

SHELX
TmcAL
XDS
MASCOT
Coot
PHENIX
RESOLVE

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