CO₂-sensitive tRNA modification associated with human mitochondrial disease.

ABSTRACT: It has been generally thought that tRNA modifications are stable and static, and their frequencies are rarely regulated. N⁶-threonylcarbamoyladenosine (t⁶A) occurs at position 37 of five mitochondrial (mt-)tRNA species. We show that YRDC and OSGEPL1 are responsible for t⁶A37 formation, utilizing L-threonine, ATP, and CO₂/bicarbonate as substrates. OSGEPL1-knockout cells exhibit respiratory defects and reduced mitochondrial translation. We find low level of t⁶A37 in mutant mt-tRNA isolated from the MERRF-like patient's cells, indicating that lack of t⁶A37 results in pathological consequences. Kinetic measurements of t⁶A37 formation reveal that the Km value of CO₂/bicarbonate is extremely high (31 mM), su

SUBMITTER: Lin H 

PROVIDER: S-EPMC5951830 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature