The Effect of tRNA^[Ser]Sec Isopentenylation on Selenoprotein Expression.

ABSTRACT: Transfer RNA^[Ser]Sec carries multiple post-transcriptional modifications. The A37G mutation in tRNA^[Ser]Sec abrogates isopentenylation of base 37 and has a profound effect on selenoprotein expression in mice. Patients with a homozygous pathogenic p.R323Q variant in tRNA-isopentenyl-transferase (TRIT1) show a severe neurological disorder, and hence we wondered whether selenoprotein expression was impaired. Patient fibroblasts with the homozygous p.R323Q variant did not show a general decrease in selenoprotein expression. However, recombinant human TRIT1^R323Q had significantly diminished activities towards several tRNA substrates in vitro. We thus engineered mice conditionally deficient in Trit1 in hepatocytes and neurons. Mass-spectrometry reve

SUBMITTER: Fradejas-Villar N 

PROVIDER: S-EPMC8583801 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature