#11743 query about threonylcarbamoyladenosine biosynthesis

[Valerie Wood]

This paper
http://www.nature.com/nchembio/journal/v9/n2/abs/nchembio.1137.html

implies that threonylcarbamoyladenosine biosynthesis occurs whilst the nucleotide is part of the tRNA molecule

and hence that
GO:0072670 mitochondrial tRNA threonylcarbamoyladenosine modification
and
GO:0070526 threonylcarbamoyladenosine biosynthetic process

are the same thing.

And therefore that
threonylcarbamoyladenosine biosynthetic process
should not be a descendent of
GO:0046085 adenosine metabolic process
(which refers to free adenosine metabolism, not adenosine as part of a nucleic acid)

[Valerie Wood]

This 2010 review implies that only
queuosine and pseudouridine, modifications occur via replacement of a nucleotide
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802272/

the other replacements are via modification of existing necleotide?

[Harold J. Drabkin]

If GO:0070526 can occur outside of the mitochondria, then no they are not the same.
However, you are right; the target is the residue in the tRNA

[Valerie Wood]

Thanks Harold!

So in this case we would need to create a new term:
1. GONEW tRNA threonylcarbamoyladenosine modification
and merge GO:0070526 threonylcarbamoyladenosine biosynthetic process into this term, and remove the small molecule nucleotide metabolism parents (or obsolete and recommend the new term as replacement)

[Valerie Wood]

Scrubbed the second part of the previous post. I was thinking of a different modification.

Would be useful to find out if tRNA threonylcarbamoyladenosine modification is only found in mitochondrial tRNAs. Do you know anyone who would know?

[Harold J. Drabkin]

N6-threonylcarbamoyladenosine (t6A) is a universally conserved, essential modified nucleoside found in transfer RNAs (tRNAs) responsible for ANN codons in all three domains of life (Nature Chemical Biology 9, 105–111 (2013)
NOT just in mitochondria.

[Tanya Berardini]

Does threonylcarbamoyladenosine only occur in tRNAs? If so, do we really need a new term or can we just modify the name of the existing GO:0070526 to include the tRNA string?

[Harold J. Drabkin]

I can find no literature indicating existence of free threonylcarbamoyladenosine.
I suppose it could exist if a trna is broken down to nmps, but not sure what would happen to it afterwards. It's not "salvaged" like some modified nucs.

[Tanya Berardini]

threonylcarbamoyladenosine biosynthetic process
should not be a descendent of
GO:0046085 adenosine metabolic process

What do you think, Harold?

So, proposed edits would be:

1. rename GO:0070526 threonylcarbamoyladenosine biosynthetic process as tRNA threonylcarbamoyladenosine biosynthetic process and add tRNA threonylcarbamoyladenosine modification as synonym

2. NEED ADVICE: remove the adenosine metabolic process parent of GO:0070526. We could add parent 'purine ribonucleoside metabolic process' instead because threonylcarbamoyladenosine is_a purine ribonucleoside in ChEBI. However, if, as Harold says, threonylcarbamoyladenosine doesn't exist in the free state, then should is be a purine ribonucleoside in ChEBI? Probably not, eh? This means we need to ask ChEBI to edit their ontology as well.

[Valerie Wood]

For 2, I think we just remove the parent?

When nucleotides/nucleosides as part of nucleic acids are metabolised they do not usually have this parentage because it refers to the free nucleotides (it has parentage to small molecule metabolism : The chemical reactions and pathways involving small molecules, any low molecular weight, monomeric, non-encoded molecule.). By analogy modification of nucleotides in DNA do not become annotated to "nucleotide metabolism"

I think the CHEBI part is OK, it is still a purine ribonucleoside incorporated into nucleic acid, just not part of purine ribonucleoside metabolism.

Thats why it might be clearer if the primary name was
tRNA threonylcarbamoyladenosine modification instead

[Valerie Wood]

Would make it a term merge

GO:0002949 tRNA threonylcarbamoyladenosine modification

v

[Tanya Berardini]

Yes, thanks Val, merge GO:0070526 into GO:0002949 and have the primary term name be 'tRNA threonylcarbamoyladenosine modification'.

Let's see what the reasoner then infers with respect to 'purine nucleoside metabolism' and figure out whether or not we need to involve ChEBI after that.

[Valerie Wood]

sounds good!

[Tanya Berardini]

Breaking the link between threonylcarbamoyladenosine metabolic process and adenosine metabolic process left that term without an is_a parent and the inferred parent based on ChEBI structure will be purine ribonucleoside metabolic process. This means that GO:0002949 is still going to have parentage going up to small molecule metabolism. We need to involve ChEBI to change their relationship between threonylcarbamoyladenosine and purine ribonucleoside.

Harold - do you know what the convention is for referring to ribonucleosides that are incorporated into RNA?

I'm going to commit the merge because it does make things slightly better (no more duplicate terms) but will leave this issue open until we resolve the parentage to 'small molecule metabolism.'

[Valerie Wood]

Can't it just be is_a tRNA modification?

[Tanya Berardini]

I can add the 'tRNA modification' parent but the small molecule parentage will appear once the reasoner runs and takes the ChEBI parentage into account.

[Valerie Wood]

Ok got it.
Presumable ChEBI will be happy to fix now it has tRNA threonylcarbamoyladenosine modification rather than just threonylcarbamoyladenosine?

[Tanya Berardini]

I've requested a new term 'tRNA threonylcarbamoyladenosine' to represent the threonylcarbamoyladenosine that's incorporated into a tRNA molecule.

You have successfully submitted tRNA threonylcarbamoyladenosine. tRNA threonylcarbamoyladenosine has been assigned ChEBI identifier CHEBI:86026. It will be available online either shortly or on your specified release date.

[Tanya Berardini]

From ChEBI:

Dear Submitter,

We are writing to inform you that your submission:

submission: 8452
chebi_id: CHEBI:86026
name: tRNA threonylcarbamoyladenosine

has now been fully curated by a member of the ChEBI team and will be available on: 06 Jul 2015 and be part of our released files on: 06 Jul 2015.
If you have any queries regarding this submission, please E-mail ChEBI-help: chebi-help@ebi.ac.uk

Thank you for submitting,
- ChEBI Team.

[Tanya Berardini]

I think this should do it:
[Term]
id: GO:0070525
-name: threonylcarbamoyladenosine metabolic process
+name: tRNA threonylcarbamoyladenosine metabolic process
namespace: biological_process
-def: "The chemical reactions and pathways involving threonylcarbamoyladenosine, a modified nucleoside found in some tRNA molecules." [GOC:imk, GOC:mah, PMID:19287007]
+def: "The chemical reactions and pathways involving tRNA threonylcarbamoyladenosine, a modified nucleoside found in some tRNA molecules." [GOC:imk, GOC:mah, PMID:19287007]
synonym: "t6A metabolic process" EXACT [PMID:19287007]
synonym: "t6A metabolism" EXACT [PMID:19287007]
synonym: "threonylcarbamoyladenosine metabolism" EXACT [GOC:MAH]
-is_a: GO:0046128 ! purine ribonucleoside metabolic process
+is_a: GO:0016070 ! RNA metabolic process
+intersection_of: GO:0008152 ! metabolic process
+intersection_of: has_participant CHEBI:86026 ! tRNA threonylcarbamoyladenosine

I'm going to close this. We can reopen if there are issues that arise.