mRNA decapping terms

[sjm41]

@pgaudet I just noticed some outstanding issues resulting from the work we did on 'mRNA decapping' MF terms in #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:

• change the parent of GO:0140933 to "is_a: GO:0016462 ! pyrophosphatase activity"

2. 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:

• change the parent of GO:0140932 to "is_a: GO:0016462 ! pyrophosphatase activity"

====

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 #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 #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 #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]

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]

The different decapping activities are nicely described/shown in PMID:30345629, which includes this figure:

[ValWood]

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]

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 #17594 xsd:anyURI
created_by: kmv
creation_date: 2019-07-08T15:55:11Z

[sjm41]

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