MRM2 (human, Q9UI43) review notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Scope: de novo review of human MRM2 (FTSJ2), the characterised mitochondrial member of
PANTHER subfamily PTHR10920:SF18, which will serve as the experimental reference for the
DROME/Mrm2 ortholog. ProtNLM2 output was not consulted.

Deep research status

just deep-research-falcon human MRM2 --fallback perplexity-lite failed: falcon returned
"Edison API request failed: Failed to authenticate", and the perplexity-lite fallback hit
its 600 s timeout. No deep-research file was produced. The review is based on the cached
primary literature (publications/), the UniProt record and the PTHR10920 PAINT table.

Evolutionary placement

• UniProt: PANTHER; PTHR10920:SF18; RRNA METHYLTRANSFERASE 2, MITOCHONDRIAL; HAMAP
  MF_01547 (RNA_methyltr_E) and "RNA methyltransferase RlmE family", i.e. the
  FtsJ/RlmE/RrmJ clade that 2'-O-methylates the A-loop uridine of LSU rRNA.
• PAINT (interpro/panther/PTHR10920/PTHR10920-paint.tsv): node PTN000100455 carries
  GO:0008650 (seeds SGD Mrm2 S000003104, E. coli RlmE P0C0R7, human MRM2), GO:0000027
  (seeds fly FBgn0038737, RlmE, human MRM2) and GO:0031167 (SGD, human). PTN000100456
  carries GO:0005739 (seeds mouse Mrm2 MGI:1915267, SGD Mrm2, human MRM2). Human MRM2 is
  itself a seed for all four IBD statements, so its IBA rows are inherited claims for
  which the target also has direct experimental grounding (not circular).

What is experimentally established in human (vs inferred)

Established in human cells:
- Mitochondrial (matrix) localisation: endogenous protein cofractionates with matrix
mtSSB1 and is proteinase K protected PMID:25009282; foci near mtDNA nucleoids
PMID:24036117.
- Site of action: Um1369 of 16S mt-rRNA (U3039 in mtDNA numbering) in the A-loop
[PMID:25074936 DNAzyme assay; PMID:25009282; PMID:35177605 RNA LC-MS2 and
transcriptome-wide 2'-O-Me profiling in MRM2 KO cells]. Catalytic residues K59 and D154
(RlmE K38/D124 equivalents): K59A and D154A abolish the modification PMID:35177605.
- MRM3-dependent Gm1370 and MRM2-dependent Um1369 are interdependent PMID:35177605.
- Catalysis-independent assembly-factor role in mtLSU biogenesis: KO causes accumulation
of immature mtLSU with disordered domains IV/V and bound MALSU1:L0R8F8:mtACP; K59A and
D154A rescue mitochondrial translation PMID:35177605.
- MRM2 is bound to late mtLSU assembly intermediates in cryo-EM structures (GTPBP5 KO
intermediates) PMID:34135318; MTERF4/NSUN4 expose the A-loop for MRM2
[PMID:34135320 abstract].
- GTPBP5 (MTG2) promotes Um1369 installation; GTPBP5 interacts with MRM2
PMID:32652011.
- Disease: homozygous p.Gly189Arg causes a MELAS-like syndrome (MTDPS17); yeast mrm2
equivalent fails to complement respiration PMID:28973171.

Inferred (not established for human MRM2 directly): the precise SAM-binding mode from the
SGC crystal structure (2NYU) is experimental, but the "proton acceptor" active site K194
in UniProt is by similarity to RlmE (ECO:0000250).

Annotation decisions (summary)

• Nucleolus (IDA, PMID:11827451): REMOVE. Contradicted by all later work; the nucleolar
  signal came from an N-terminally GFP-tagged construct, which masks the N-terminal
  mitochondrial targeting sequence PMID:24036117.
• mitochondrion (6 rows) -> MODIFY to mitochondrial matrix (GO:0005759), which the gene
  already carries and which fractionation supports.
• rRNA processing, rRNA methylation, methyltransferase activity, ribosomal LSU assembly:
  MODIFY to the specific terms the gene carries (GO:0000451, GO:0008650, GO:1902775).
• No NEW annotations. Mitochondrial translation and respiration defects in KO cells and
  the Drosophila developmental arrest are downstream consequences of an mtLSU assembly
  defect, not process participation.