TRNT1 UniProt Q96Q11

1 alternative isoform · canonical 434 aa · mitochondrion; cytosol

TRNT1 encodes the CCA-adding enzyme essential for maturation of both cytoplasmic and mitochondrial tRNAs, and biallelic loss-of-function mutations cause the multisystem SIFD syndrome [PMID:25193871]. The enzyme adds the CCA trinucleotide to tRNA 3' ends in both compartments; in patient cells with reduced TRNT1, CCA addition is selectively impaired for the non-canonical mitochondrial tRNA(Ser(AGY)), and complete knockdown renders this tRNA undetectable and abolishes synthesis of mitochondrial polypeptides containing Ser(AGY) codons while sparing those that lack them [PMID:25652405]. Impaired CCA addition extends to other mt-tRNAs including tRNA(Cys), tRNA(LeuUUR) and tRNA(His) [PMID:27370603], and the downstream consequence is reduced abundance of select OXPHOS complex proteins with decreased basal and maximal cellular respiration, the disease mutations leaving TRNT1 subcellular localization intact [PMID:27317422]. Beyond defective mitochondrial translation, TRNT1 deficiency triggers a broader stress program: angiogenin-dependent tRNA fragmentation, eIF2α phosphorylation, elevated reactive oxygen species, and altered translation of specific proteins [PMID:37239403], together with autophagy defects (aberrant LC3-II accumulation) in patient-derived retinal organoids [PMID:28390992] and an augmented ER stress response in activated T cells [PMID:30758723]. Loss-of-function is causal in vivo: morpholino suppression of trnt1 in zebrafish recapitulates anemia, sensory organ defects, and dose-dependent visual dysfunction that is rescued by human TRNT1 RNA [PMID:26494905].