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NTR: mRNA cap methyltransferase RNMT:RAMAC complex #26548

Closed Antonialock closed 8 months ago

Antonialock commented 10 months ago

Please provide as much information as you can:

A protein complex that consists of RAMAC and RNMT and is involved in mRNA cap methylation.

methyltransferase complex

it looks different from the existing mRNA cap methyltransferase complex

raymond91125 commented 10 months ago

RNMT and RAMAC are both annotated with GO:0031533 mRNA cap methyltransferase complex. How is this new complex different? We would like to make the distinction clear. @ValWood What do you think?

Antonialock commented 10 months ago

RAMAC is not a mRNA guanylyltransferase, it doesn't seem to have any enzymatic activity ?

The def for mRNA cap methyltransferase complex says "A protein complex that consists of an RNA 5' triphosphatase and a guanyl transferase "

Message ID: @.***>

ValWood commented 10 months ago

I haven't looked much at this but

1. https://www.pombase.org/term_genes/GO:0006370 7-methylguanosine mRNA capping (GO:0006370) is a mutistep process see https://github.com/geneontology/go-ontology/issues/26464

Cap synthesis entails three enzymatic reactions: (i) the 5′ triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA triphosphatase; (ii) the diphosphate RNA end is capped with GMP by RNA guanylyltransferase; and (iii) the GpppN cap is methylated by RNA (guanine-N7) methyltransferase (1).

  1. RNMT is the RNA (guanine-N7) methyltransferase

This paper seems to confirm https://pubmed.ncbi.nlm.nih.gov/29719263/ mRNA Cap Methyltransferase, RNMT-RAM, Promotes RNA Pol II-Dependent Transcription

(note to self, I haven't annotated pcm1 to mRNA cap methyltransferase complex , only to P-TEFb-cap methyltransferase complex , possibly in error)

ValWood commented 10 months ago
  1. Yes something is weird here, @Antonialock is correct

mRNA cap methyltransferase complex (GO:0031533)

Definition Parents

A protein complex that consists of an RNA 5' triphosphatase and a guanyl transferase (Cet1p and Ceg1p in S. cerevisiae; Pct1 and Ceg1 in S. pombe) and is involved in mRNA capping. [PMID:10347220]

Definition Parents A protein complex that consists of an RNA 5' triphosphatase and a guanyl transferase (Cet1p and Ceg1p in S. cerevisiae; Pct1 and Ceg1 in S. pombe) and is involved in mRNA capping. [PMID:10347220]

@sjm41 did you look at these recently? Is this definition of mRNA cap methyltransferase complex correct, or is it defined differently for yeast and metazoa

ValWood commented 10 months ago

This looks useful https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(19)30002-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0968000419300027%3Fshowall%3Dtrue

and shows how the complexes are recruited to the pol II CTD, the problem is that there are multiple complexes that could be described as mRNA CAP methyltransferases. These need to be disambiguated. I would name them after the principal activity with "mRNA cap methyltransferase" as a related synonym

Screenshot 2023-12-05 at 08 29 56

@pgaudet

pgaudet commented 10 months ago

Hi @ValWood - I see you tagged me - how can I help?

ValWood commented 10 months ago

I wondered if you had any input, but probably @raymond91125 can take it from here. It seems the existing term labels and defs just need to be more precise.

raymond91125 commented 10 months ago

To summarize:

  1. For mRNA capping, there are two activities RNA guanylyltransferase and 5' phospatase encoded by a single gene in vertebrates (RNGTT), worm (cel-1), and fly (mRNA-cap), but by two genes in the yeasts acting in a complex.
  2. For mRNA cap methylation in mammals, there is a complex of RNA guanine-7 methyltransferase (RNMT) and RNA guanine-7 methyltransferase activating subunit (RAMAC).
ValWood commented 10 months ago

  1. I see ceg1/pct1, it is a single subunit in human. I didn't spot that.

  2. mRNA (guanine-N7) methyltransferase complex is an exact synonym of mRNA cap methyltransferase complex (GO:0031533), the names could just be swapped.

  3. Functionally RNMT:RAMAC is mRNA (guanine-N7) methyltransferase complex, just that in higher eukaryotes there is an additional regulatory subunit. in GO we would not create a separate complex for that, but make RNMT:RAMAC complex a narrow synonym, and adjust the definition to say there is an additional subunit in human. (possibly RAM is present in yeast but with sequence similarity is low. I' have a look for it).

raymond91125 commented 10 months ago

[Term] id: GO:0160130 name: mRNA cap methyltransferase RNMT:RAMAC complex namespace: cellular_component def: "A protein complex that consists of RNA guanine-7 methyltransferase (RNMT) and RNA guanine-7 methyltransferase activating subunit (RAMAC) and is involved in mRNA cap methylation." [PMID:22099306] is_a: GO:0034708 ! methyltransferase complex property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/26548" xsd:anyURI created_by: rynl creation_date: 2023-12-08T01:33:31Z

raymond91125 commented 10 months ago

@ValWood I am now quite confused. I renamed GO:0031533 to "mRNA capping enzyme complex". Is this not correct? That's what the definition says. Therefore, GO:00315333 is not "mRNA cap methyltransferase complex", nor "mRNA (guanine-N7) methyltransferase complex"

What it is now: [Term] id: GO:0031533 name: mRNA capping enzyme complex def: "A protein complex that consists of an RNA 5' triphosphatase and a guanyl transferase (Cet1p and Ceg1p in S. cerevisiae; Pct1 and Ceg1 in S. pombe) and is involved in mRNA capping." [GOC:vw, PMID:10347220, PMID:12455993, PMID:9345280]

raymond91125 commented 10 months ago

@ValWood Are you saying that this new term should not be made?

[Term] id: GO:0160130 name: mRNA cap methyltransferase RNMT:RAMAC complex namespace: cellular_component def: "A protein complex that consists of RNA guanine-7 methyltransferase (RNMT) and RNA guanine-7 methyltransferase activating subunit (RAMAC) and is involved in mRNA cap methylation." [PMID:22099306] is_a: GO:0034708 ! methyltransferase complex property_value: term_tracker_item "#26548" xsd:anyURI created_by: rynl creation_date: 2023-12-08T01:33:31Z

ValWood commented 10 months ago

Hi @raymond91125 I think this term is fine. The pombe and S. cerevisiae RNMT are single subunit. I suspect that is because we have not detected RAMAC yet. It isn't very conserved.

I agree that the name of GO:0031533 is confusing and I agree it should not mention methyltransferase. I think this is a conflation because it is involved in methyl cap formation. In fact, in fission yeast these 2 enzymes do not even form a complex....they seem to be independent.

raymond91125 commented 10 months ago

Thanks, @ValWood

Antonialock commented 8 months ago

@raymond91125 Should this term be available now? I cannot see it in amigo? Thanks

raymond91125 commented 8 months ago

Very weird. It appears that the created term has not gotten in although the git log says it did. https://github.com/geneontology/go-ontology/pull/26604/commits/1a60a0930416f7b029c86756c01d7f27666d503d

raymond91125 commented 8 months ago

Added back. Thanks for the alert. @Antonialock