New. 08/2023

The mammalian tRNA ligase complex (tRNA‐LC)

The mammalian tRNA ligase complex (tRNA‐LC) was found by the Martinez Lab to catalyze the splicing of intron‐containing pre‐tRNAs in the nucleus and the splicing of XBP1 mRNA during the unfolded protein response (UPR) in the cytoplasm.
Very recently, the Lab also reported that the tRNA‐LC co‐evolved with PYROXD1, an essential oxidoreductase that protects the catalytic cysteine
of RTCB, the catalytic subunit of the tRNA‐LC, against aerobic oxidation.
The current study, published as open access in the journal “RNA” shows that the oxidoreductase Thioredoxin (TRX) preserves the enzymatic activity of RTCB under otherwise inhibiting concentrations of oxidants. TRX physically interacts with oxidized RTCB and both reduces and
re‐activates RTCB through the action of its redox‐active cysteine pair.

The publication further shows that TRX interacts with RTCB at late stages of UPR, and since the interaction requires oxidative conditions, the findings of the Martinez Lab suggest that prolonged UPR generates reactive oxygen species.

Together, the reported results support a functional role for TRX in securing and repairing the active site of the tRNA‐LC, thereby allowing pre‐tRNA splicing and UPR to occur when cells encounter mild, but still inhibitory levels of reactive oxygen species.


www.rnajournal.cshlp.org/content/early/2023/08/30/rna.079732.123.full.pdf+html