gtpbp3 encodes the mitochondrial tRNA-modification GTPase GTPBP3 (TrmE/MnmE family), a nuclear-encoded, transit-peptide-targeted matrix protein that forms, with Mto1, the enzyme installing the 5-taurinomethyl group on the wobble uridine (U34) of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). Its GTP hydrolysis, together with the Mto1 catalytic subunit, is required for the modification, which shapes the anticodon loop and supports accurate decoding during mitochondrial translation. In zebrafish all three isoforms localise to mitochondria; knock-out larvae show altered mt-tRNA conformation and aminoacylation, mildly reduced tRNALys, impaired synthesis of mtDNA-encoded OXPHOS subunits, proteostasis stress and hypertrophic cardiomyopathy, modelling GTPBP3-associated human cardiomyopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoplasm (is_active_in) from the family-wide node PTN000182687, whose donors include bacterial MnmE (cytoplasmic) alongside mitochondrial eukaryotic members. Reason: Gtpbp3 carries a mitochondrial transit peptide (UniProt TRANSIT 1-73) and all three zebrafish isoforms localise to mitochondria [PMID:27184967]; mitochondrion is part_of cytoplasm, so the node-level term is not false, but the informative location is the mitochondrion, annotated by IDA/IBA/ISS. Kept as non-core rather than removed. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000182687 SUPPORTS TRANSFER Family node spanning bacterial cytoplasmic MnmE and mitochondrial eukaryotic orthologs; cytoplasm is the common denominator, mitochondrion the informative term for the zebrafish target. Supporting Evidence: PMID:27184967 Zebrafish gtpbp3 has three isoforms localized at mitochondria. file:DANRE/gtpbp3/gtpbp3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0002098 tRNA wobble uridine modification | IBA GO_REF:0000033 | ACCEPT | Summary: Trna wobble uridine modification: the taurinomethyl-U34 modification of mt-tRNAGlu/Gln/Lys/Trp/Leu(UUR) catalysed by the GTPBP3-MTO1 complex. Reason: PAINT node PTN000182687 (MnmE/TrmE family; E. coli MnmE, yeast Mss1, human GTPBP3) - the wobble-uridine 5-substitution is the ancestral function of this family, and the zebrafish knock-out phenotype [PMID:30916346] is consistent. Core process. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion: nuclear-encoded, transit-peptide-bearing matrix enzyme; all three zebrafish isoforms localise to mitochondria. Reason: PAINT node PTN000746268 (eukaryotic GTPBP3/Mss1 subnode) consistent with the transit peptide and the zebrafish isoform localisation [PMID:27184967]. Core location. Supporting Evidence: PMID:27184967 Zebrafish gtpbp3 has three isoforms localized at mitochondria. file:DANRE/gtpbp3/gtpbp3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0030488 tRNA methylation | IBA GO_REF:0000033 | MODIFY | Summary: tRNA methylation, from the MnmE-family PAINT node PTN000182687 seeded by E. coli MnmE. Reason: The MnmE/GTPBP3 complex does not add a methyl group: in bacteria MnmE-MnmG installs (carboxymethyl)aminomethyl-U34 and in mitochondria GTPBP3-MTO1 installs taurinomethyl-U34, a C5-CH2-taurine substituent whose methylene comes from methylene-THF (UniProt FUNCTION; [PMID:30916346]). 'tRNA methylation' therefore mis-describes the chemistry at the node and for the zebrafish target; the accurate term, GO:0070899 mitochondrial tRNA wobble uridine modification, is already annotated (ISS). Modify. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000182687 SUPPORTS SOURCE BUT NOT TARGET MnmE/TrmE family node; the U34 5-substituent installed by this family is a (carboxymethyl)aminomethyl or taurinomethyl group, not a methyl group, so the term is chemically imprecise at the node. UniProtKB:P25522 Β· mnmE SOURCE WEAK OR INFERRED E. coli MnmE donor; MnmE-MnmG forms cmnm5U/nm5U, the methylation to mnm5U is carried out by MnmC. Proposed replacements: mitochondrial tRNA wobble uridine modification Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GTPase activity: Gtpbp3 is the TrmE-family G-domain subunit whose GTP hydrolysis is required, with MTO1, for taurinomethyl-U34 formation. Reason: InterPro MnmE signature (IPR004520) mapping; UniProt records the Rhea GTP hydrolysis reaction and the requirement of GTPBP3 GTPase activity for the modification (by similarity). No zebrafish GTPase assay, but the conserved G domain (residues 248-422, GTP-binding motifs) and the knock-out modification phenotype [PMID:30916346] make this the core molecular function. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt Reaction=GTP + H2O = GDP + phosphate + H(+) file:DANRE/gtpbp3/gtpbp3-uniprot.txt Taum(5)U formation on mammalian mt-tRNA requires the presence of both GTPBP3-mediated GTPase activity and MTO1 catalytic activity. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: GTP binding from the MnmE/G-domain InterPro signatures; UniProt annotates the G1-G4 GTP-binding motifs (255-262, 281-285, 302-305, 373-376). Reason: Entailed by the GTPase activity and correct, but a substrate-binding descriptor rather than the function; kept as non-core. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt Reaction=GTP + H2O = GDP + phosphate + H(+) file:DANRE/gtpbp3/gtpbp3-uniprot.txt Taum(5)U formation on mammalian mt-tRNA requires the presence of both GTPBP3-mediated GTPase activity and MTO1 catalytic activity. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrion: nuclear-encoded, transit-peptide-bearing matrix enzyme; all three zebrafish isoforms localise to mitochondria. Reason: SubCell/ARBA mapping consistent with the transit peptide and the zebrafish isoform localisation [PMID:27184967]. Core location. Supporting Evidence: PMID:27184967 Zebrafish gtpbp3 has three isoforms localized at mitochondria. file:DANRE/gtpbp3/gtpbp3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006400 tRNA modification | IEA GO_REF:0000002 | MODIFY | Summary: tRNA modification, generic parent from the MnmE InterPro signature (IPR004520). Reason: Correct but broad; the specific process supported by the UniProt FUNCTION and the zebrafish knock-out [PMID:30916346] is mitochondrial tRNA wobble uridine modification, already annotated. Modify to GO:0070899. Proposed replacements: mitochondrial tRNA wobble uridine modification Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0070900 mitochondrial tRNA modification | IEA GO_REF:0000117 | ACCEPT | Summary: Mitochondrial tRNA modification: Gtpbp3 is the GTPase subunit of the GTPBP3-MTO1 complex that installs taurinomethyl-U34 on mt-tRNAs. Reason: ARBA mapping (ARBA00086089) consistent with the UniProt FUNCTION and with [PMID:30916346]. The enzyme complex performs the modification step, so this is a core process; the more specific wobble-uridine child is also annotated. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). PMID:30916346 The aberrant mitochondrial tRNA metabolisms impaired mitochondrial translation, produced proteostasis stress and altered activities of respiratory chain complexes. |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: GTPase activity: Gtpbp3 is the TrmE-family G-domain subunit whose GTP hydrolysis is required, with MTO1, for taurinomethyl-U34 formation. Reason: Transfer from human GTPBP3 (Q969Y2); UniProt records the Rhea GTP hydrolysis reaction and the requirement of GTPBP3 GTPase activity for the modification (by similarity). No zebrafish GTPase assay, but the conserved G domain (residues 248-422, GTP-binding motifs) and the knock-out modification phenotype [PMID:30916346] make this the core molecular function. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt Reaction=GTP + H2O = GDP + phosphate + H(+) file:DANRE/gtpbp3/gtpbp3-uniprot.txt Taum(5)U formation on mammalian mt-tRNA requires the presence of both GTPBP3-mediated GTPase activity and MTO1 catalytic activity. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrion: nuclear-encoded, transit-peptide-bearing matrix enzyme; all three zebrafish isoforms localise to mitochondria. Reason: Transfer from human GTPBP3 (Q969Y2) consistent with the transit peptide and the zebrafish isoform localisation [PMID:27184967]. Core location. Supporting Evidence: PMID:27184967 Zebrafish gtpbp3 has three isoforms localized at mitochondria. file:DANRE/gtpbp3/gtpbp3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0070899 mitochondrial tRNA wobble uridine modification | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial trna wobble uridine modification: the taurinomethyl-U34 modification of mt-tRNAGlu/Gln/Lys/Trp/Leu(UUR) catalysed by the GTPBP3-MTO1 complex. Reason: Transfer from human GTPBP3 (Q969Y2), consistent with the zebrafish knock-out phenotype [PMID:30916346]. Core process. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). |
| GO:0036416 tRNA stabilization | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | KEEP AS NON CORE | Summary: tRNA stabilization (prevention of tRNA degradation), IMP from the knock-out: steady-state tRNALys mildly reduced, other mt-tRNAs unchanged [PMID:30916346]. Reason: Full text read. U34 modification contributes to anticodon-loop structure, and the knock-out shows altered nuclease sensitivity of the unmodified tRNAs, but the effect on steady-state levels is confined to a mild reduction of tRNALys; Gtpbp3 does not itself protect tRNA from nucleases. Downstream consequence of the core modification activity, kept as non-core. Supporting Evidence: PMID:30916346 The steady-state levels of tRNALys was mildly reduced in gtpbp3β/β zebrafish, but the levels of tRNAGlu, tRNAGln, tRNATrp, tRNALeu(UUR) and tRNAAla from gtpbp3 mutant zebrafish were all comparable with those in WT zebrafish. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070143 obsolete mitochondrial alanyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial alanyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. file:DANRE/gtpbp3/gtpbp3-deep-research-falcon.md gtpbp3KO zebrafish showed increased efficiencies of tRNA aminoacylation**, and that mt-tRNA instability signatures discussed for Mto1 deficiency were reported as similar to those in gtpbp3-related models. |
| GO:0070153 obsolete mitochondrial leucyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial leucyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070154 obsolete mitochondrial lysyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial lysyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070155 obsolete mitochondrial methionyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial methionyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070183 obsolete mitochondrial tryptophanyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial tryptophanyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070184 obsolete mitochondrial tyrosyl-tRNA aminoacylation | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | REMOVE | Summary: Mitochondrial tyrosyl-tRNA aminoacylation (term now obsolete in GO, no replacement). IMP from gtpbp3 knock-out zebrafish, in which aminoacylation of this mt-tRNA was measured. Reason: Full text read. Aminoacylation is performed by the mitochondrial aminoacyl-tRNA synthetase, not by Gtpbp3; the knock-out shows a global INCREASE in aminoacylated fractions, which the authors attribute to the altered conformation of unmodified tRNAs [PMID:30916346], i.e. an indirect consequence of losing the U34 taurinomethyl modification, not participation in charging. The term itself is obsolete (QuickGO), so the row cannot be retained as-is; the observation is already covered by the accepted mitochondrial tRNA modification IMP from the same paper. Removal does not dispute the measurement. Supporting Evidence: PMID:30916346 Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. PMID:30916346 These data validated that the inactivation of Gtpbp3 changed the conformation of mitochondrial tRNAs. |
| GO:0070900 mitochondrial tRNA modification | IMP PMID:30916346 Deletion of Gtpbp3 in zebrafish revealed the hypertrophic ca... | ACCEPT | Summary: Mitochondrial tRNA modification: Gtpbp3 is the GTPase subunit of the GTPBP3-MTO1 complex that installs taurinomethyl-U34 on mt-tRNAs. Reason: Zebrafish knock-out shows the expected loss-of-modification phenotype - altered tRNA conformation, altered aminoacylation and impaired mitochondrial translation - [PMID:30916346]. The enzyme complex performs the modification step, so this is a core process; the more specific wobble-uridine child is also annotated. Supporting Evidence: file:DANRE/gtpbp3/gtpbp3-uniprot.txt GTPase component of the GTPBP3-MTO1 complex that catalyzes the 5-taurinomethyluridine (taum(5)U) modification at the 34th wobble position (U34) of mitochondrial tRNAs (mt-tRNAs), which plays a role in mt-tRNA decoding and mitochondrial translation. PMID:30916346 GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of Οm5U at the wobble position of mitochondrial tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). PMID:30916346 The aberrant mitochondrial tRNA metabolisms impaired mitochondrial translation, produced proteostasis stress and altered activities of respiratory chain complexes. |
| GO:0005739 mitochondrion | IDA PMID:27184967 The defective expression of gtpbp3 related to tRNA modificat... | ACCEPT | Summary: Mitochondrion: nuclear-encoded, transit-peptide-bearing matrix enzyme; all three zebrafish isoforms localise to mitochondria. Reason: Direct localisation in zebrafish (abstract-only cache, but the abstract states it). Core location. Supporting Evidence: PMID:27184967 Zebrafish gtpbp3 has three isoforms localized at mitochondria. file:DANRE/gtpbp3/gtpbp3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0048568 embryonic organ development | IMP PMID:27184967 The defective expression of gtpbp3 related to tRNA modificat... | KEEP AS NON CORE | Summary: Embryonic organ development, IMP from two gtpbp3 morpholinos: bleeding, oedema, pigmentation and tail-curvature defects by 5 dpf [PMID:27184967]. Reason: Abstract only in the cache, but the abstract states the morphant phenotype. Gtpbp3 does no work in organogenesis; the defects follow from impaired mitochondrial translation and OXPHOS after loss of mt-tRNA modification [PMID:30916346]. Downstream phenotype, kept as non-core for both morpholino rows. Supporting Evidence: PMID:27184967 The Gtpbp3 morphants exhibited defective in embryonic development including bleeding, melenin, oedema and curved tails within 5days post fertilization, as compared with uninjected controls. PMID:30916346 The aberrant mitochondrial tRNA metabolisms impaired mitochondrial translation, produced proteostasis stress and altered activities of respiratory chain complexes. |
| GO:0048568 embryonic organ development | IMP PMID:27184967 The defective expression of gtpbp3 related to tRNA modificat... | KEEP AS NON CORE | Summary: Embryonic organ development, IMP from two gtpbp3 morpholinos: bleeding, oedema, pigmentation and tail-curvature defects by 5 dpf [PMID:27184967]. Reason: Abstract only in the cache, but the abstract states the morphant phenotype. Gtpbp3 does no work in organogenesis; the defects follow from impaired mitochondrial translation and OXPHOS after loss of mt-tRNA modification [PMID:30916346]. Downstream phenotype, kept as non-core for both morpholino rows. Supporting Evidence: PMID:27184967 The Gtpbp3 morphants exhibited defective in embryonic development including bleeding, melenin, oedema and curved tails within 5days post fertilization, as compared with uninjected controls. PMID:30916346 The aberrant mitochondrial tRNA metabolisms impaired mitochondrial translation, produced proteostasis stress and altered activities of respiratory chain complexes. |
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Download this section (compressed HTML)Q: Is the taurinomethyl-U34 modification itself lost in gtpbp3 knock-out zebrafish mt-tRNAs (by mass spectrometry), as opposed to the 2-thiouridylation and conformational read-outs reported?
Q: Does zebrafish Gtpbp3 require Mto1 for activity, and does an mto1 knock-out phenocopy the gtpbp3 cardiomyopathy?
Experiment: LC-MS/MS nucleoside analysis of purified mt-tRNALys and mt-tRNALeu(UUR) from wild-type, gtpbp3+/- and gtpbp3-/- zebrafish hearts to quantify Οm5U and Οm5s2U directly.
Hypothesis: Gtpbp3 loss abolishes Οm5U34 on mt-tRNAs in zebrafish, as in human GTPBP3-deficient cells.
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