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Matrix: ribosome metabolic process/ cofactor metabolic process (Question?) #2482

Closed ValWood closed 10 months ago

ValWood commented 5 years ago

Hi @pgaudet wasn't there a decision at some point that we didn't annotate methyltransferases to " S-adenosylmethionine biosynthetic process" because this is just the interconverting methyl donor ? (this is actually the only one I came across so far)

METTL16 | RNA N6-adenosine-methyltransferase METTL16 |   | S-adenosylmethionine biosynthetic process |   | UniProt | Homo sapiens | IDA |   | sam-dependent methyltransferase pthr13393 | protein |   | PMID:28525753 | 20181030

  | METTL16 | RNA N6-adenosine-methyltransferase METTL16 |   | S-adenosylmethionine biosynthetic process |   | UniProt | Homo sapiens | IDA |   | sam-dependent methyltransferase pthr13393 | protein |   | PMID:30197297 | 20181030

ValWood commented 5 years ago

There is also PAINT nmapping rmt2 | N-methyltransferase (predicted) |   | S-adenosylhomocysteine metabolic process |   | GO_Central | Schizosaccharomyces pombe | IBA | PANTHER:PTN001282244RGD:2659 | family not named pthr32379 | protein |   | PMID:21873635

pgaudet commented 5 years ago

@sylvainpoux Can you look at the 'S-adenosylmethionine biosynthetic process' annotations for Q86W50?

sylvainpoux commented 5 years ago

Hi Pascale,

I would say that the S-adenosylmethionine biosynthetic process is correct as this methyltransferase directly regulates expression of MAT2A.

As it represents the main role of this enzyme and as there is no term for regulation of S-adenosylmethionine biosynthetic process, it is the only way to capture this. Removing this annotation would remove the most important process regulated by this protein

Sylvain

ValWood commented 5 years ago

OK got it rmt2 is directly regulating SAM biosynthesis via the regulation of MAT2A splicing.

mettl16

To capture the contribution of METTL16 in the methylation cycle I would probably do:

METTL16 rRNA (adenine-N6-)-methyltransferase activity has_input MAT2A * part_of "GO:1905869 "negative regulation of 3'-UTR-mediated mRNA stabilization" PMID:28525753

(i.e methylates the MAT2A mRNA and destabilizes it for breakdown)

AND METTL16 GO:0003729 mRNA binding has_input MAT2A* part_of "GO:0070935 3'-UTR-mediated mRNA stabilization", part_of "NTR positive regulation of S-adenosylmethionine biosynthetic process" PMID:28525753

(i.e binds the MAT2A mRNA and allows it to translate SAM synthetase )

This makes it clear that METTL16 is performing 2 separate activities, and one is regulates S-adenosylmethionine biosynthetic process via the control of MAT2A expression.

I thought the annotation was from the reaction adenosine in U6 snRNA + S-adenosyl-L-methionine = H+ + N6-methyladenosine in U6 snRNA + S-adenosyl-L-homocysteine (which would be incorrect anyway because its consuming S-adenosyl-L-methionine)

(* or could use the Ensembl transcript ID. At Pombase we just use the gene ID which isn't ideal, but the substrate type can be inferred from the term)

sylvainpoux commented 5 years ago

Thanks I will use GO:1905869 term as well, regarding GO:0006556, I used the qualifier acts_upstream to indicate that it is not directly part of the biosynthesis

ValWood commented 5 years ago

This sounds like a good use of "acts_upstream_of"

I wonder instead of part_of "GO:0070935 3'-UTR-mediated mRNA stabilization", if the process for this one should be GO:0048026 positive regulation of mRNA splicing, via spliceosome

(the stabilization terms bother me a bit because they are just an output of the enhanced splicing, so it lead to inconsistent annotation a similar issue was identified with "protein stabilization, and the proposal was obsoletion https://github.com/geneontology/go-ontology/issues/16360)

The "positive regulation of mRNA splicing, via spliceosome" give the more correct parent to "positive regulation of gene expression"