id: A7UX10 gene_symbol: NCU11362 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:367110 label: Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) description: NCU11362 is a METTL16-family RNA N6-adenosine methyltransferase inferred to modify U6 snRNA using S-adenosylmethionine. The conserved U6 modification promotes accurate pre-mRNA splice-site recognition. Nuclear RNA modification is strongly supported by fungal ortholog experiments; a distinct Neurospora mRNA methylation repertoire is unresolved. existing_annotations: - term: &id003 id: GO:0000398 label: mRNA splicing, via spliceosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - PANTHER:PTN000333540 - PomBase:SPAC27D7.08c review: summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. action: ACCEPT reason: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. Fission yeast mtl16 deletion causes intron retention, providing a mechanistic basis for transfer of splicing and post-transcriptional regulation to this METTL16 homolog. supported_by: - reference_id: PMID:34050143 supporting_text: We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. - term: id: GO:0001734 label: mRNA m(6)A methyltransferase activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - MGI:MGI:1914743 - PANTHER:PTN000333540 - UniProtKB:Q86W50 - WB:WBGene00014228 review: summary: The curated ancestral assertion predicts mRNA methylation, but METTL16 substrate repertoires differ among eukaryotes. action: UNDECIDED reason: The curated ancestral assertion predicts mRNA methylation, but METTL16 substrate repertoires differ among eukaryotes. The verified fungal experiments establish U6 methylation and consequent mRNA splicing, which do not by themselves show methyl-group transfer to mRNA. Neurospora mRNA substrate recognition or a resolved fungal-clade substrate analysis is needed to adjudicate this more specific activity. supported_by: - reference_id: PMID:34050143 supporting_text: We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. - reference_id: PMID:29051200 supporting_text: 'We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA' propagation_review: root_cause: UNRESOLVED source_entities: - source_id: PANTHER:PTN000333540 source_status: UNRESOLVED comment: This PAINT node asserts inherited METTL16 mRNA methylation. Fungal U6 experiments support the family and RNA methylation, but do not resolve whether the mRNA-substrate property was retained in Neurospora. The node placement for this particular substrate remains unadjudicated; donor count is not the issue. - term: &id005 id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - AGI_LocusCode:AT2G21070 - PANTHER:PTN000333540 - UniProtKB:Q86W50 - WB:WBGene00014228 review: summary: U6 snRNA modification and the resulting spliceosomal role support a conserved nuclear function for this METTL16-family protein. action: ACCEPT reason: U6 snRNA modification and the resulting spliceosomal role support a conserved nuclear function for this METTL16-family protein. This is a family-based localization inference, not Neurospora microscopy. supported_by: - reference_id: PMID:29051200 supporting_text: 'We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA' - reference_id: PMID:34050143 supporting_text: We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. - term: id: GO:0008168 label: methyltransferase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables supporting_entities: - ARBA:ARBA00028302 - InterPro:IPR010286 review: summary: Methyltransferase activity is correct but loses the supported U6 RNA substrate and N6-adenosine chemistry. action: MODIFY reason: Methyltransferase activity is correct but loses the supported U6 RNA substrate and N6-adenosine chemistry. The specific METTL16 family and characterized fungal enzyme justify the U6 methyltransferase term. supported_by: - reference_id: PMID:40841561 supporting_text: 'The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing.' proposed_replacement_terms: - id: GO:0120048 label: U6 snRNA (adenine(43)-N6)-methyltransferase activity - term: id: GO:0010608 label: post-transcriptional regulation of gene expression evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:1914743 - PANTHER:PTN000333540 - UniProtKB:Q86W50 - WB:WBGene00014228 review: summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. action: ACCEPT reason: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. Fission yeast mtl16 deletion causes intron retention, providing a mechanistic basis for transfer of splicing and post-transcriptional regulation to this METTL16 homolog. supported_by: - reference_id: PMID:34050143 supporting_text: We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. - term: &id004 id: GO:0120048 label: U6 snRNA (adenine(43)-N6)-methyltransferase activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - PANTHER:PTN000333540 - PomBase:SPAC27D7.08c - UniProtKB:Q86W50 - WB:WBGene00014228 review: summary: The METTL16-specific family placement supports conserved U6 adenosine N6 methylation. action: ACCEPT reason: The METTL16-specific family placement supports conserved U6 adenosine N6 methylation. Fission yeast Mtl16 has direct biochemical and structural support for the same chemistry; human A43 corresponds to the homologous U6 site, not a newly established Neurospora nucleotide number. The curated ancestral assertion is consistent with this conserved substrate recognition. supported_by: - reference_id: PMID:40841561 supporting_text: 'The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing.' - reference_id: PMID:29051200 supporting_text: 'We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA' - &id001 reference_id: file:NEUCR/NCU11362/NCU11362-uniprot.txt supporting_text: DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1. - term: &id002 id: GO:0001510 label: RNA methylation evidence_type: ISS original_reference_id: PMID:40841561 review: summary: U6 adenosine methylation is an RNA methylation process. action: NEW reason: U6 adenosine methylation is an RNA methylation process. This conserved METTL16 function follows from specific family placement and fungal biochemical evidence without transferring a mammalian mRNA substrate. supported_by: - reference_id: PMID:40841561 supporting_text: 'The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing.' - *id001 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:34050143 title: A single m(6)A modification in U6 snRNA diversifies exon sequence at the 5' splice site. full_text_unavailable: false - id: PMID:29051200 title: Human METTL16 is a N(6)-methyladenosine (m(6)A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. full_text_unavailable: false - id: PMID:40841561 title: Structures and mechanisms of U6 snRNA m(6)A modification by METTL16. full_text_unavailable: false - id: file:NEUCR/NCU11362/NCU11362-uniprot.txt title: 'UniProt record for NCU11362: domain and family evidence' core_functions: - description: NCU11362 is a METTL16-family RNA N6-adenosine methyltransferase inferred to modify U6 snRNA using S-adenosylmethionine. The conserved U6 modification promotes accurate pre-mRNA splice-site recognition. Nuclear RNA modification is strongly supported by fungal ortholog experiments; a distinct Neurospora mRNA methylation repertoire is unresolved. supported_by: - reference_id: PMID:40841561 supporting_text: 'The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing.' - reference_id: PMID:34050143 supporting_text: We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. - reference_id: file:NEUCR/NCU11362/NCU11362-uniprot.txt supporting_text: DR InterPro; IPR010286; METTL16/RlmF. - *id001 directly_involved_in: - *id002 - *id003 molecular_function: *id004 locations: - *id005