NTR: tRNA N1-methyladenine (m1A58) demethylase activity

[ValWood]

Please provide as much information as you can:

• Suggested term label: tRNA N1-methyladenine (m1A58) demethylase activity I am not quite sure how the label should be constructed?

• Definition (free text)

Catalysis of the removal of N1-methyladenine from position 58 (m1A58) of a tRNA molecule.

• Reference, in format PMID:####### PMID:27745969

• Gene product name and ID to be annotated to this term

https://www.pombase.org/gene/SPBC13G1.04c (by ISS) https://www.uniprot.org/uniprotkb/Q13686/entry (@Antonialock )

• Parent term(s)

tRNA demethylase activity (GO:1990984)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

current thinking according to Uniprot:

Mainly acts as a tRNA demethylase by removing N1-methyladenine from various tRNAs, with a preference for N1-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969).

but this protein does not have the specific term annotated

I was annotating a pombe paper PMID:35901126 which described ALKBH1 as a

and I wanted to ISS to it.

[ValWood]

@sjm41 @pgaudet doe this name/label look OK? I can't locate anything in Rhea for tRNA demethylases?

[sjm41]

I see the methyltranferase reaction (https://www.rhea-db.org/rhea/43152) but not the demethylase reaction per se in RHEA. I guess the demethylase reaction is different from the methyltranferase reaction in the reverse direction?? That is, would RHEA actually make a separate reaction for the demethylase?

[ValWood]

I think so, it's a different enzyme (like histone demethylases) . Will check if there is a reason @amorgat @kaxelsen

[deustp01]

it's a different enzyme

And probably a different reaction entirely, i.e., SAM methyl donor input to methylation reaction is not regenerated by the demethylation one?

[kaxelsen]

Correct, the demethylation takes place by a dioxygenase reaction, i.e., O2 is used to kick off the methyl group that is liberated as formaldehyde

[kaxelsen]

A general demethylase reaction is6 RHEA:54576 2-oxoglutarate + an N1-methyladenosine in tRNA + O2 = an adenosine in tRNA + CO2 + formaldehyde + succinate

We have now also created RHEA:79019 2-oxoglutarate + N1-methyladenosine58 in tRNA + O2 = adenosine58 in tRNA + CO2 + formaldehyde + succinate It will become publicly available in release 2024_03 scheduled for May 22

[ValWood]

Thank you @kaxelsen

[pgaudet]

Hi @ValWood

Discussing with @kaxelsen here in Geneva - This is a very non-specific dioxygenase/demethylase; should we create terms for all substrates? On the other hand, the methylases seem more specific.

[ValWood]

It's OK I can use "tRNA demethylase activity (GO:1990984)" if you think this is the more appropriate level (or whatever you suggest).