Mrm2 (CG11447) encodes the Drosophila mitochondrial rRNA methyltransferase 2, a nuclear-encoded precursor with an N-terminal mitochondrial targeting sequence and a single FtsJ/RlmE-family class I SAM-dependent methyltransferase domain. It belongs to the same PANTHER subfamily as bacterial RlmE and human MRM2, which 2'-O-methylate a universally conserved uridine in the A-loop of the large-subunit rRNA peptidyl transferase centre, and it retains the catalytic lysine and SAM-binding residues of those enzymes. Human MRM2 also acts as a late-stage assembly factor for the mitochondrial ribosome large subunit, a role that does not need its methyltransferase activity. In flies, RNAi knockdown of Mrm2 causes developmental delay, late-pupal lethality and reduced respiratory-chain subunit levels, and muscle-specific knockdown impairs locomotion, consistent with a requirement in mitochondrial ribosome biogenesis. The fly modification site and enzyme activity have not been measured directly.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000027 ribosomal large subunit assembly | IBA GO_REF:0000033 | MODIFY | Summary: Correct but general; the assembled particle is the mitochondrial large subunit. Reason: The PAINT assertion at PTN000100455 joins bacterial RlmE and mitochondrial MRM2. For this mitochondrially targeted member, the supported specific term is mitochondrial large ribosomal subunit assembly (GO:1902775), which the gene already carries by FlyBase IMP. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000100455 SUPPORTS TRANSFER Eukaryotic-scoped node in PTHR10920:SF18 joining RlmE and MRM2; the ancestral assembly role transfers correctly, but for a mitochondrially targeted member the mitochondrial LSU term is the precise one. UniProtKB:Q9UI43 SUPPORTS TRANSFER Human MRM2 mtLSU assembly evidence (PMID:35177605). FB:FBgn0038737 SUPPORTS TRANSFER The target's own FlyBase IMP among the seeds; expected, not circular. Proposed replacements: mitochondrial large ribosomal subunit assembly Supporting Evidence: PMID:35177605 The catalytic activity of MRM2 is dispensable for mtLSU biogenesis PMID:35177605 we knocked-down the MRM2 D. melanogaster orthologue CG11447 file:DROME/Mrm2/Mrm2-uniprot.txt FT TRANSIT 1..35 |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mrm2 is a mitochondrially targeted rRNA methyltransferase. Reason: The predicted 1-35 transit peptide and orthology to human MRM2 (same PANTHER subfamily PTHR10920:SF18; PAINT node PTN000100456) place Mrm2 in mitochondria. Endogenous fly protein has not been localised, so the organelle-level term is as precise as the direct evidence allows; the matrix row records the finer compartment. Supporting Evidence: file:DROME/Mrm2/Mrm2-uniprot.txt FT TRANSIT 1..35 PMID:35177605 Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mrm2 is a mitochondrially targeted rRNA methyltransferase. Reason: The predicted 1-35 transit peptide and orthology to human MRM2 (same PANTHER subfamily PTHR10920:SF18; PAINT node PTN000100456) place Mrm2 in mitochondria. Endogenous fly protein has not been localised, so the organelle-level term is as precise as the direct evidence allows; the matrix row records the finer compartment. Supporting Evidence: file:DROME/Mrm2/Mrm2-uniprot.txt FT TRANSIT 1..35 PMID:35177605 Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mrm2 is a mitochondrially targeted rRNA methyltransferase. Reason: The predicted 1-35 transit peptide and orthology to human MRM2 (same PANTHER subfamily PTHR10920:SF18; PAINT node PTN000100456) place Mrm2 in mitochondria. Endogenous fly protein has not been localised, so the organelle-level term is as precise as the direct evidence allows; the matrix row records the finer compartment. Supporting Evidence: file:DROME/Mrm2/Mrm2-uniprot.txt FT TRANSIT 1..35 PMID:35177605 Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. |
| GO:0005759 mitochondrial matrix | IC PMID:35177605 A late-stage assembly checkpoint of the human mitochondrial ... | ACCEPT | Summary: Mitochondrial matrix is the compartment of mitoribosome assembly. Reason: FlyBase inferred matrix from the mtLSU assembly role. Mitoribosome biogenesis and mt-rRNA modification take place in the matrix, so this is a sound curator inference, although fly sub-mitochondrial localisation has not been measured. Supporting Evidence: PMID:35177605 The catalytic activity of MRM2 is dispensable for mtLSU biogenesis file:DROME/Mrm2/Mrm2-uniprot.txt FT TRANSIT 1..35 |
| GO:0006364 rRNA processing | ISS PMID:35177605 A late-stage assembly checkpoint of the human mitochondrial ... | MODIFY | Summary: True but general; the specific process is rRNA methylation. Reason: rRNA processing is entailed by rRNA methylation (GO:0031167), which the gene already carries by IBA and which describes the reaction Mrm2 performs. Mrm2 is not known to cleave rRNA. Assembly is captured separately by GO:1902775. Proposed replacements: rRNA methylation Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: General methyltransferase term; the specific activity is rRNA uridine 2'-O-ribose methylation. Reason: The InterPro FtsJ/RlmE signatures place Mrm2 in the RlmE family, whose members are rRNA (uridine-2'-O-ribose)-methyltransferases; the gene already carries GO:0008650. Proposed replacements: rRNA (uridine-2'-O-ribose)-methyltransferase activity Supporting Evidence: file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase |
| GO:0008650 rRNA (uridine-2'-O-ribose)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved rRNA uridine 2'-O-methyltransferase activity, inferred by orthology. Reason: Mrm2 is in PTHR10920:SF18 with E. coli RlmE and human MRM2, the seeds of the eukaryotic PAINT node PTN000100455 that carries this function, and it retains the RlmE catalytic lysine (K201) and all experimentally defined SAM-binding residues. Activity is inferred: no fly enzyme assay or methylation mapping exists, and the human nucleotide position should not be read as a fly coordinate. Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md are conserved in Q9VDT6 (G91, W93, D119, D136, D161) |
| GO:0008650 rRNA (uridine-2'-O-ribose)-methyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Conserved rRNA uridine 2'-O-methyltransferase activity, inferred by orthology. Reason: Mrm2 is in PTHR10920:SF18 with E. coli RlmE and human MRM2, the seeds of the eukaryotic PAINT node PTN000100455 that carries this function, and it retains the RlmE catalytic lysine (K201) and all experimentally defined SAM-binding residues. Activity is inferred: no fly enzyme assay or methylation mapping exists, and the human nucleotide position should not be read as a fly coordinate. Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md are conserved in Q9VDT6 (G91, W93, D119, D136, D161) |
| GO:0008650 rRNA (uridine-2'-O-ribose)-methyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Conserved rRNA uridine 2'-O-methyltransferase activity, inferred by orthology. Reason: Mrm2 is in PTHR10920:SF18 with E. coli RlmE and human MRM2, the seeds of the eukaryotic PAINT node PTN000100455 that carries this function, and it retains the RlmE catalytic lysine (K201) and all experimentally defined SAM-binding residues. Activity is inferred: no fly enzyme assay or methylation mapping exists, and the human nucleotide position should not be read as a fly coordinate. Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md are conserved in Q9VDT6 (G91, W93, D119, D136, D161) |
| GO:0008650 rRNA (uridine-2'-O-ribose)-methyltransferase activity | ISS PMID:35177605 A late-stage assembly checkpoint of the human mitochondrial ... | ACCEPT | Summary: Conserved rRNA uridine 2'-O-methyltransferase activity, inferred by orthology. Reason: Mrm2 is in PTHR10920:SF18 with E. coli RlmE and human MRM2, the seeds of the eukaryotic PAINT node PTN000100455 that carries this function, and it retains the RlmE catalytic lysine (K201) and all experimentally defined SAM-binding residues. Activity is inferred: no fly enzyme assay or methylation mapping exists, and the human nucleotide position should not be read as a fly coordinate. Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md are conserved in Q9VDT6 (G91, W93, D119, D136, D161) |
| GO:0031167 rRNA methylation | IBA GO_REF:0000033 | ACCEPT | Summary: rRNA methylation is the process the methyltransferase activity carries out. Reason: Propagated from PTN000100455 with the activity term. It follows directly from the conserved rRNA 2'-O-methyltransferase function and is as specific as the PAINT node warrants. Supporting Evidence: PMID:35177605 MRM2 is also a S -adenosyl methionine (SAM)-dependent 2′- O -ribose methyltransferase file:DROME/Mrm2/Mrm2-uniprot.txt RNA methyltransferase RlmE family file:DROME/Mrm2/Mrm2-bioinformatics/RESULTS-rereview.md maps to Q9VDT6 K201 (conserved) |
| GO:1902775 mitochondrial large ribosomal subunit assembly | IMP PMID:35177605 A late-stage assembly checkpoint of the human mitochondrial ... | ACCEPT | Summary: Mitochondrial large-subunit assembly is a core, catalysis-independent role. Reason: FlyBase curated this from PMID:35177605. The fly experiments show developmental arrest and reduced respiratory-chain subunits after knockdown, but did not assay mitoribosome assembly directly. Assembly itself was shown for the human ortholog, which is in the same PANTHER subfamily and under the same PAINT node, and does not need catalysis. Deferring to the curator. Supporting Evidence: PMID:35177605 The catalytic activity of MRM2 is dispensable for mtLSU biogenesis PMID:35177605 we knocked-down the MRM2 D. melanogaster orthologue CG11447 PMID:35177605 Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. file:DROME/Mrm2/Mrm2-deep-research-falcon.md The study did not directly measure fly mitochondrial ribosome assembly, the fly rRNA methylation site, or fly mitochondrial translation rates. |
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Download this section (compressed HTML)Q: Which nucleotide of Drosophila mt:lrRNA corresponds to the human MRM2 target uridine, and is it 2'-O-methylated in a Mrm2-dependent way?
Q: Does fly Mrm2, like human MRM2, support mitochondrial large-subunit assembly independently of its catalytic activity?
Experiment: Map 2'-O-methylation of mt:lrRNA by RiboMeth-seq or LC-MS/MS in control and Mrm2-knockdown or null flies, and assay recombinant Mrm2 on fly mt-rRNA substrates.
Hypothesis: Mrm2 installs the conserved A-loop uridine 2'-O-methylation in fly mt:lrRNA.
Experiment: Rescue Mrm2 RNAi or null animals with wild-type or K201A transgenes; measure mtLSU/mtSSU sedimentation, mitochondrial translation and respiratory-chain levels.
Hypothesis: Catalytically dead Mrm2 (K201A) rescues fly development and mtLSU assembly.
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