NCU11362

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000398 mRNA splicing, via spliceosome	IBA GO_REF:0000033	ACCEPT	Summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. 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. Supporting Evidence: PMID:34050143 We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.
GO:0001734 mRNA m(6)A methyltransferase activity	IBA GO_REF:0000033	UNDECIDED	Summary: The curated ancestral assertion predicts mRNA methylation, but METTL16 substrate repertoires differ among eukaryotes. 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. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000333540 UNRESOLVED 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. Supporting Evidence: PMID:34050143 We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA. PMID:29051200 We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: U6 snRNA modification and the resulting spliceosomal role support a conserved nuclear function for this METTL16-family protein. 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. Supporting Evidence: PMID:29051200 We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA PMID:34050143 We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.
GO:0008168 methyltransferase activity	IEA GO_REF:0000120	MODIFY	Summary: Methyltransferase activity is correct but loses the supported U6 RNA substrate and N6-adenosine chemistry. 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. Proposed replacements: U6 snRNA (adenine(43)-N6)-methyltransferase activity Supporting Evidence: PMID:40841561 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.
GO:0010608 post-transcriptional regulation of gene expression	IBA GO_REF:0000033	ACCEPT	Summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing. 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. Supporting Evidence: PMID:34050143 We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.
GO:0120048 U6 snRNA (adenine(43)-N6)-methyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: The METTL16-specific family placement supports conserved U6 adenosine N6 methylation. 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. Supporting Evidence: PMID:40841561 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. PMID:29051200 We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA file:NEUCR/NCU11362/NCU11362-uniprot.txt DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1.
GO:0001510 RNA methylation	ISS PMID:40841561 Structures and mechanisms of U6 snRNA m(6)A modification by ...	NEW	Summary: U6 adenosine methylation is an RNA methylation process. 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. Supporting Evidence: PMID:40841561 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. file:NEUCR/NCU11362/NCU11362-uniprot.txt DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1.

GO Term

Evidence

Action

Reason

GO:0000398 mRNA splicing, via spliceosome

IBA
GO_REF:0000033

Summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing.

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.

Supporting Evidence:

PMID:34050143

We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.

GO:0001734 mRNA m(6)A methyltransferase activity

IBA
GO_REF:0000033

UNDECIDED

Summary: The curated ancestral assertion predicts mRNA methylation, but METTL16 substrate repertoires differ among eukaryotes.

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.

Propagation Review

Root cause: UNRESOLVED

Sources checked:

PANTHER:PTN000333540 UNRESOLVED

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.

Supporting Evidence:

PMID:34050143

We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.

PMID:29051200

We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA

GO:0005634 nucleus

IBA
GO_REF:0000033

Summary: U6 snRNA modification and the resulting spliceosomal role support a conserved nuclear function for this METTL16-family protein.

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.

Supporting Evidence:

PMID:29051200

We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA

PMID:34050143

We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.

GO:0008168 methyltransferase activity

IEA
GO_REF:0000120

MODIFY

Summary: Methyltransferase activity is correct but loses the supported U6 RNA substrate and N6-adenosine chemistry.

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.

Proposed replacements: U6 snRNA (adenine(43)-N6)-methyltransferase activity

Supporting Evidence:

PMID:40841561

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.

GO:0010608 post-transcriptional regulation of gene expression

IBA
GO_REF:0000033

Summary: METTL16-dependent U6 methylation modulates splice-site recognition and pre-mRNA processing.

Supporting Evidence:

PMID:34050143

We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.

GO:0120048 U6 snRNA (adenine(43)-N6)-methyltransferase activity

IBA
GO_REF:0000033

Summary: The METTL16-specific family placement supports conserved U6 adenosine N6 methylation.

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.

Supporting Evidence:

PMID:40841561

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.

PMID:29051200

We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA

file:NEUCR/NCU11362/NCU11362-uniprot.txt

DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1.

GO:0001510 RNA methylation

ISS
PMID:40841561
Structures and mechanisms of U6 snRNA m(6)A modification by ...

NEW

Summary: U6 adenosine methylation is an RNA methylation process.

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.

Supporting Evidence:

PMID:40841561

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.

file:NEUCR/NCU11362/NCU11362-uniprot.txt

DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1.

Core Functions

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.

Molecular Function:

U6 snRNA (adenine(43)-N6)-methyltransferase activity

Directly Involved In:

RNA methylation mRNA splicing, via spliceosome

Cellular Locations:

nucleus

Supporting Evidence:

PMID:40841561
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.
PMID:34050143
We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA.
file:NEUCR/NCU11362/NCU11362-uniprot.txt
DR InterPro; IPR010286; METTL16/RlmF.
file:NEUCR/NCU11362/NCU11362-uniprot.txt
DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · NCU11362-protnlm-predictions-review.yaml · Review status: COMPLETE

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.

Source documents: genes/NEUCR/NCU11362/NCU11362-protnlm-source.json · genes/NEUCR/NCU11362/NCU11362-uniprot.txt · genes/NEUCR/NCU11362/NCU11362-ai-review.yaml

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0044238 primary metabolic process GO_BP

LSP — Less precise than existing annotation Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-09 · file:NEUCR/NCU11362/NCU11362-protnlm-source.json

Review rationale: Specific METTL16 subfamily placement and characterized fungal U6 methylation establish an RNA primary-metabolism role. The U6 methyltransferase activity and RNA methylation process are more informative than primary metabolic process. RNA methylation (GO:0001510) is a biological-process descendant of the emitted term, so LSP reflects a supported difference in process specificity. The inference concerns conserved RNA modification, not the bacterial RlmF 23S rRNA substrate.

Supporting Evidence:

PMID:40841561: "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."
PMID:34050143: "We found that a subset of introns was retained in mRNAs, indicating a splicing defect caused by loss of m6A in U6 snRNA."
file:NEUCR/NCU11362/NCU11362-uniprot.txt: "DR InterPro; IPR010286; METTL16/RlmF."
file:NEUCR/NCU11362/NCU11362-uniprot.txt: "DR PANTHER; PTHR13393:SF0; RNA N6-ADENOSINE-METHYLTRANSFERASE METTL16; 1."

Gene Description

Existing Annotations Review

Core Functions

References

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

📚 Additional Documentation

Notes

📄 View Raw YAML