MT-TL1 encodes mitochondrial tRNA-Leu(UUR), one of the 22 transfer RNAs encoded by mitochondrial DNA (on the heavy strand, between the 16S rRNA and ND1 genes). After processing from the polycistronic transcript, it is charged with leucine by the mitochondrial leucyl-tRNA synthetase and, in the mitochondrial matrix, acts as the adaptor that reads the leucine UUA and UUG codons of the 13 mtDNA-encoded mRNAs on the mitoribosome. Its anticodon wobble uridine carries a nuclear-enzyme-installed 5-taurinomethyl modification that is required for efficient UUG decoding. Pathogenic variants, most often m.3243A>G, cause MELAS and maternally inherited diabetes and deafness; the mutant tRNA is less abundant, less efficiently aminoacylated and lacks the wobble taurine modification, giving a codon-biased defect in mitochondrial translation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006412 translation | IEA GO_REF:0000108 | MODIFY | Summary: Electronic inference from the adaptor MF (GO:0030533 part_of translation). Correct, but MT-TL1 is a mitochondrial-genome tRNA that functions only in mitochondrial translation. Reason: The tRNA participates directly in translation (it performs the codon-reading adaptor step), so the process is right; the specific process for an mtDNA-encoded tRNA read on the mitoribosome is mitochondrial translation (GO:0032543, is_a translation). Proposed replacements: mitochondrial translation Supporting Evidence: PMID:15477592 the WT mt tRNA Leu(UUR) was efficient in decoding both the UUA and UUG codons and showed no activity with the UUC noncognate codon. PMID:12549915 The combined effects of the reductions in the steady-state levels and the aminoacylated fraction of tRNA(Leu(UUR)) are likely to contribute to the decreases in the rates of mitochondrial translation observed in mutant cells. |
| GO:0030533 triplet codon-amino acid adaptor activity | IEA GO_REF:0000115 | ACCEPT | Summary: Rfam2GO assignment of the canonical tRNA molecular function. Direct experimental support exists for MT-TL1 decoding its cognate leucine UUA and UUG codons. Reason: This is the core molecular function of a tRNA, and the tRNA itself carries it out (codon-anticodon pairing at the ribosomal A site with its aminoacyl end positioned for peptide bond formation). Wild-type mt tRNA-Leu(UUR) decodes UUA and UUG, but not UUC, in a mitochondrial translation system. Supporting Evidence: PMID:15477592 the WT mt tRNA Leu(UUR) was efficient in decoding both the UUA and UUG codons and showed no activity with the UUC noncognate codon. PMID:15477592 Native mt tRNA Leu(UUR) efficiently bound to both the UUA and UUG codons |
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Download this section (compressed HTML)Q: Should GO curators annotate mtDNA-encoded tRNAs (RNAcentral ids) directly to mitochondrial translation rather than relying on the generic Rfam-derived translation inference?
Suggested experts: GO RNA annotation curators
Q: Does the reduced UUA decoding seen with native m.3243A>G tRNA (beyond the UUG defect of an unmodified wild-type tRNA) reflect the D-loop mutation's effect on tRNA structure, ribosome interaction, or EF-Tu binding?
Suggested experts: mitochondrial translation biochemists
Experiment: Mitoribosome profiling in m.3243A>G cybrids at graded heteroplasmy to quantify UUG versus UUA codon-specific stalling in each mtDNA-encoded mRNA.
Hypothesis: Translation of UUG-rich mtDNA ORFs (notably ND subunits) is preferentially stalled, explaining complex I deficiency in MELAS.
Type: ribosome profiling
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