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Source ontology files for the Gene Ontology
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mRNA decapping terms #24892

Closed sjm41 closed 9 months ago

sjm41 commented 1 year ago

@pgaudet I just noticed some outstanding issues resulting from the work we did on 'mRNA decapping' MF terms in https://github.com/geneontology/go-ontology/issues/23290. Might be easier to VC about this - let me know.

There are four terms concerned, and their current relationships (under pyrophosphatase activity) look like this:

pyrophosphatase activity (GO:0016462) . mRNA 5'-phosphatase activity (GO:0140818, EC:3.6.1.74) ... 5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity (GO:0140933, EC:3.6.1.62) . mRNA 5'-diphosphatase activity (GO:0034353, no EC) ... 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity (GO:0140932, EC:3.6.1.59)

I think this needs to be changed so all 4 terms are direct children of 'pyrophosphatase activity', i.e. to look like this: pyrophosphatase activity (GO:0016462) . mRNA 5'-phosphatase activity (GO:0140818, EC:3.6.1.74) . 5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity (GO:0140933, EC:3.6.1.62) . mRNA 5'-diphosphatase activity (GO:0034353, no EC) . 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity (GO:0140932, EC:3.6.1.59)

Here's my reasoning, with the current GO entries shown at the bottom.

  1. Currently, we have "5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity" (GO:0140933) is_a "mRNA 5'-phosphatase activity" (GO:0140818)

Two problems here: i) The parent activity (GO:0140818) removes one phosphate to produce a diphospho-mRNA, whereas the child term (GO:0140933) removes two phosphates to produce a monophospho-mRNA ii) The EC entry (EC:3.6.1.74) xreffed to the parent (GO:0140818) says that this enzyme is involved in mRNA capping, and the only human SP entry annotated with this EC is O60942/RNGTT "mRNA-capping enzyme". Whereas the child term (GO:0140933/EC:3.6.1.62) describes a decapping activity, typically carried out by Q8IU60/DCP2 "m7GpppN-mRNA hydrolase"

Solution:

  1. Currently, we have "5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity" (GO:0140932) is_a "mRNA 5'-diphosphatase activity" (GO:0034353)

Similar (but the opposite situation) to above, the problem here is that the parent activity (GO:0034353) removes diphosphate to produce a monophospho-mRNA (typically performed by O77932/DXO "Decapping and exoribonuclease protein"), whereas the child term (GO:0140932/EC:3.6.1.59) removes one phosphate to produce a diphospho-mRNA (performed by Q96C86/DCPS "m7GpppX diphosphatase")

Solution:

====

id: GO:0140818 name: mRNA 5'-phosphatase activity namespace: molecular_function def: "A 5'-end triphospho-[mRNA] + H2O = a 5'-end diphospho-[mRNA] + H+ + phosphate." [PMID:9473487] synonym: "mRNA 5'-triphosphate monophosphatase activity" EXACT [] xref: EC:3.6.1.74 xref: RHEA:67004 is_a: GO:0016462 ! pyrophosphatase activity is_a: GO:0140098 ! catalytic activity, acting on RNA property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23319 xsd:anyURI created_by: pg creation_date: 2022-05-16T06:01:07Z

id: GO:0140933 name: 5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity namespace: molecular_function def: "Catalysis of the reaction: a 5'-end (N7-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + H2O = a 5'-end phospho-ribonucleoside in mRNA + N7-methyl-GDP + H+." [PMID:18820299, PMID:29483298] synonym: "m(7)GpppN-mRNA hydrolase activity" EXACT [] xref: EC:3.6.1.62 xref: RHEA:67484 is_a: GO:0140818 ! mRNA 5'-phosphatase activity property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23290 xsd:anyURI created_by: pg creation_date: 2022-10-24T15:48:42Z

id: GO:0034353 name: mRNA 5'-diphosphatase activity namespace: molecular_function def: "Catalysis of the removal of a 5' terminal diphosphate from the 5'-triphosphate end of an mRNA, leaving a 5'-monophosphate end." [GOC:jh2, PMID:17612492, PMID:18202662] synonym: "RNA pyrophosphohydrolase activity" BROAD [] is_a: GO:0016462 ! pyrophosphatase activity is_a: GO:0140098 ! catalytic activity, acting on RNA property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23401 xsd:anyURI

id: GO:0140932 name: 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity namespace: molecular_function def: "Catalysis of the reaction: a 5'-end (N2,N2,N7-trimethyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + H2O = a 5'-end diphospho-ribonucleoside in mRNA + 2 H+ + N7-methyl-GMP. Can also use (N7-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA as a substrate." [PMID:24742626, PMID:32723815] synonym: "m(7)GpppN m(7)GMP phosphohydrolase activity" EXACT [EC:3.6.1.59] synonym: "m(7)GpppX diphosphatase activity" EXACT [EC:3.6.1.59] synonym: "m(7)GpppX pyrophosphatase activity" EXACT [EC:3.6.1.59] xref: EC:3.6.1.59 {source="skos:exactMatch"} xref: RHEA:65384 {source="skos:narrowMatch"} xref: RHEA:65388 {source="skos:narrowMatch"} is_a: GO:0034353 ! mRNA 5'-diphosphatase activity created_by: pg creation_date: 2022-10-24T15:37:32Z

sjm41 commented 1 year ago

I realise that "mRNA 5'-diphosphatase activity" (GO:0034353) and "5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity" (GO:0140933, EC:3.6.1.62/RHEA:67484) are not identical and should not be merged - I have edited the original ticket accordingly.

sjm41 commented 1 year ago

The different decapping activities are nicely described/shown in PMID:30345629, which includes this figure: Screenshot 2023-02-10 at 11 19 19

ValWood commented 1 year ago

Hi both.

I was annotating a decapping paper recently. I also found 2 other terms that seem to refer to decapping enzymes GO:0110152 RNA NAD-cap (NAD-forming) hydrolase activity and GO:1990174 | phosphodiesterase decapping endonuclease activity

Should they merge into any of the terms above terms?

sjm41 commented 1 year ago

GO:0110152 RNA NAD-cap (NAD-forming) hydrolase activity is a separate activity (labeled with 'NAD+ cap' in the figure I posted above) and the term seems good as it is.

id: GO:0110152 name: RNA NAD-cap (NAD-forming) hydrolase activity namespace: molecular_function def: "Catalysis of the reaction: a 5'-end NAD+-phospho-ribonucleoside in mRNA + H2O = a 5'-end phospho-ribonucleoside in mRNA + H+ + NAD+." [GOC:sp, PMID:28283058, RHEA:60880] comment: This reaction specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA. xref: RHEA:60880 is_a: GO:0016818 ! hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides is_a: GO:0140098 ! catalytic activity, acting on RNA property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/17594 xsd:anyURI created_by: kmv creation_date: 2019-07-08T15:55:11Z

sjm41 commented 1 year ago

GO:1990174 | phosphodiesterase decapping endonuclease activity also seems good as it is - this activity is labeled with 'unmethylated cap' (performed by Rai1/DXO) in the figure above. The article describes it as a "triphosphonucleotide hydrolase (TPH) activity" that "hydrolyse the mRNA between the first and the second transcribed nucleotide, this way producing the 5′ monophosphorylated RNA substrate"

id: GO:1990174 name: phosphodiesterase decapping endonuclease activity namespace: molecular_function def: "Catalysis of the removal of the cap from an unmethylated 5'-end capped RNA resulting in the release of the entire cap structure (GpppN) and a 5' monophosphorylated RNA." [GOC:dgf, PMID:20802481] synonym: "G(5')pppN pyrophosphatase activity" RELATED [] is_a: GO:0016891 ! RNA endonuclease activity, producing 5'-phosphomonoesters created_by: tb creation_date: 2013-08-26T17:51:00Z