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Source ontology files for the Gene Ontology
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Gene silencing by miRNA child term names #12155

Closed rachhuntley closed 6 years ago

rachhuntley commented 9 years ago

Val has pointed out that the child terms of gene silencing by miRNA have odd names.

I'm copying her comments here.

'mRNA cleavage involved in gene silencing by miRNA’ (GO:0035279) suggests that the cleavage of the target is a step in the process rather than the result of the silencing. Could be re-named to 'gene silencing by miRNA dependent mRNA cleavage'?

'deadenylation involved in gene silencing by miRNA’ (GO:0098806). Similar to above, could be renamed to 'Gene silencing by miRNA-dependent deadenylation'?

‘negative regulation of translation involved in gene silencing by miRNA’ (GO:0035278). Again sounds like the regulation of translation is involved in the silencing rather than being the endpoint. Could be re-named to 'miRNA dependent translational repression' (RH comment: or to be consistent with above 'gene silencing by miRNA-dependent translational repression')?

Any other suggestions?

@dosumis Copying David OS here as he has worked on these terms. @ValWood

rachhuntley commented 9 years ago

Changing this to high priority as I need a decision before I submit a paper later this week. Thanks.

dosumis commented 9 years ago

'mRNA cleavage involved in gene silencing by miRNA’ (GO:0035279) suggests that the cleavage of the target is a step in the process rather than the result of the silencing.

Isn't it just the final step in the process? This is reflected in the logical def too:

'mRNA cleavage involved in gene silencing by miRNA' EquivalentTo: 'mRNA cleavage' and ('part of' some 'gene silencing by miRNA')

This pattern => grouping under both 'mRNA cleavage' (via is_a) and 'gene silencing by miRNA' (via part_of).

I suppose we could define this instead as an mRNA cleavage event that is regulated_by 'gene silencing by miRNA'. But this feels wrong to me and it doesn't work for grouping under 'gene silencing by miRNA'. Als, Judging by the names, the suggested replacements don't have these semantics.

'gene silencing by miRNA dependent mRNA cleavage' suggests to me a type of gene silencing via the mechanism of 'miRNA dependent mRNA cleavage'. That mechanism could have multiple steps with the final one being cleavage, but in this case the mRNA cleavage would have a has_part relationship to the term - which obviously won't work for grouping.

The same argument applies to this suggestion:

'deadenylation involved in gene silencing by miRNA’ (GO:0098806). Similar to above, could be renamed to 'Gene silencing by miRNA-dependent deadenylation'?

TL;DR: The names are justified and will stay the same. I might consider some synonyms, but don't think your suggestions will work for these either.

(TBC: I have a different suggestion for the last name change you suggest)

dosumis commented 9 years ago

Agree that this doesn't sound great:

negative regulation of translation involved in gene silencing by miRNA

But I wonder whether we need the term. If we agree that 'gene silencing by miRNA' negatively regulates translation (either directly or by degrading transcript), then we can add relationships to 'gene silencing by miRNA' to place it in the same location in the class heirarchy as 'negative regulation of translation involved in gene silencing by miRNA'. The parent class of 'negative regulation of translation involved in gene silencing by miRNA' is"negative regulation of translation, ncRNA-mediated".

negative regulation of translation, ncRNA-mediated EquivalentTo: 'negative regulation of translation' that mediated_by some ncRNA

gene silencing by miRNA SubClassof: negatively_regulates some translation SubClassof: mediated_by some miRNA => inferred SubClassOf: 'negative regulation of translation, ncRNA-mediated'

Are you happy for me to go ahead with this?

ValWood commented 9 years ago

OK, its fine if they are defined as the final step. Its the translation one which bothers me the most... it looks the wrong way around....the others are OK

I don't think the direct child of translation would work...its not 'gene silencing by miRNA' isn't always regulating translation directly...(regulation of translation should be regulating the translation machinery?). AFAIK, this term was for miRNA silencing used in this context?

If you took the regulation of mRNA degradation as a regulation of translation, you could say the same about all RNA degradation, and even regulation of transcription. I think a separate term is still required. It seems to be a different miRNA pathway? Rachel will need to confirm.

rachhuntley commented 9 years ago

Yes, not happy with David's suggestion for the translation term. Gene silencing is regulation of gene expression, NOT regulation of translation always. Note that mRNA cleavage is under gene silencing by miRNA, and this is not affecting translation.

I would still like a separate term for the effect of miRNA on translation repression.

dosumis commented 9 years ago

'gene silencing by miRNA' isn't always regulating translation directly...(regulation of translation should be regulating the translation machinery?)

In previous discussions, we agreed that regulation of gene expression could be via regulation of transcript levels (by whatever mechanism). This allows 'gene silencing by miRNA' to be classified under 'negative regulation of gene expression'. I think that this only makes sense if 'negative regulation of translation' can also be via regulation of transcript levels. To distingish direct vs indirect, we could use the new directly_inhibits relation in RO to give a logical definition to 'negative regulation of translation involved in gene silencing by miRNA'. Here's a suggestion for that an for simplifying the name.

negative regulation of translation involved in gene silencing by miRNA -> direct inhibition of translation by miRNA def: "The process in which microRNAs (miRNAs) block the translation of target mRNAs into proteins. Once incorporated into a RNA-induced silencing complex (RISC), a miRNA will typically repress translation if the miRNA imperfectly base-pairs with the 3' untranslated regions of target mRNAs." EquivalentTO: biological regulation that (part_of some gene silencing by miRNA) and (directly_inhibits some translation) and (mediated_by some miRNA)

As before, this => grouping under 'gene silencing by miRNA' via part_of and under 'negative regulation of translation' via SubClassOf (Inferred)

If you're happy with that. I'll implement ASAP.

dosumis commented 9 years ago

Gene silencing is regulation of gene expression, NOT regulation of translation always. Note that mRNA cleavage is under gene silencing by miRNA, and this is not affecting translation.

But see my last comment: Is the distinction between direct and indirect sufficient?

rachhuntley commented 9 years ago

So are you suggesting simplifying the name to 'direct inhibition of translation by miRNA'?

I'm not sure where direct and indirect comes into this, my argument was that gene silencing by miRNA is not the same as negative regulation of translation, so you shouldn't get rid of that term and use gene silencing by miRNA instead.

dosumis commented 9 years ago

Sorry if not being clear. Here's the argument again. Hopefully stated more clearly:

Ignoring the logical defs, here's the graph:

negative regulation of translation, ncRNA-mediated . <- is_a gene silencing by miRNA . . <- part_of 'mRNA cleavage involved in gene silencing by miRNA' . . <- part_of direct inhibition of translation by miRNA

But if you think that's too confusing, I'll just do this:

gene silencing by miRNA . . <- part_of 'mRNA cleavage involved in gene silencing by miRNA' . . <- part_of 'direct inhibition of translation by miRNA'

negative regulation of translation, ncRNA-mediated . <- is_a 'direct inhibition of translation by miRNA' # Logical definition uses direct inhibition.

'gene silencing by miRNA' retains its path up 'negative regulation of gene expression'

Either way I'll improve the axiomatisation using mediated_by relationships as described above.

ValWood commented 9 years ago

Hi David,

I don't think it necessarily follows logically that because gene silencing is regulation of gene expression, that 'gene silencing by miRNA' belongs under 'negative regulation of translation'

You can regulate gene expression in lots of ways (these include regulating transcription, splicing, other mRNA processing, nuclear export, degradation, translation, or post translational processing), but they are not all regulation of translation. Imagine you have some RNAs which produce proteins which are only expressed during meiosis. These are sequestered (and possibly degraded) by some mechanism. I don't think you would expect the gene products involved in this process to be annotated to negative regulation of translation? In the same way you would not expect negative regulation of protein translation to be annotated to negative regulation of protein maturation? Negative regulation of "gene expression by microRNA" seems similar (although probably more closely linked to translation spatially and temporally) than some other processes.....

dosumis commented 9 years ago

I don't think it necessarily follows logically that because gene silencing is regulation of gene expression, that 'gene silencing by miRNA' belongs under 'negative regulation of translation'

The argument comes down to whether regulation of levels of a substrate/intermediate is a type of regulation , so I don't think your objections apply. But I'm happy to just ignore this in order to get a fix in place. How about I just go with the second option above. The main change is

negative regulation of translation involved in gene silencing by miRNA -> direct inhibition of translation by miRNA

Plus more complete classification & some improvements under the hood

rachhuntley commented 9 years ago

I think your second option would work... (if Val agrees)

gene silencing by miRNA . . <- part_of 'mRNA cleavage involved in gene silencing by miRNA' . . <- part_of 'direct inhibition of translation by miRNA'

negative regulation of translation, ncRNA-mediated . <- is_a 'direct inhibition of translation by miRNA' # Logical definition uses direct inhibition.

but I'm not sure about the name 'direct inhibition of translation by miRNA' - this appears to be saying the miRNA is inhibiting the translation directly. The miRNA is providing the target specificity, not repressing the translation directly, other factors are recruited to do this.

Can you call it 'negative regulation of translation, miRNA-mediated' instead?

ValWood commented 9 years ago

I think I can explain this with better examples. Usually the genes which are 'silenced' would not usually be expressed in the cell type/developmental stage. This is a bit like pombe genes which are silenced by siRNAs. it appears that meiotic genes are suppressed during vegetative growth using this mechanism. It therefore seems strange to say that 'translation' is negatively regulated. Translation does not occur, but there is no 'regulation' of translation per.se. The translation machinery is not being negatively regulated by this process. The regulation step (removal or inactivation of the RNA) occurs before translation (its an upstream process). I think in the process Rachel is describing, there must be some closer association with the translation machinery and a direct role in translation? is that correct?

ValWood commented 9 years ago

Sounds good to me

rachhuntley commented 9 years ago

Sorry, going into a meeting now, but see this paper http://www.nature.com/cdd/journal/v22/n1/full/cdd2014112a.html Figure 3 shows translation repression (although here it is followed by deadenylation and degradation, this doesn't always happen, it can just stop at the repression of translation stage)

dosumis commented 9 years ago

The regulation step (removal or inactivation of the RNA) occurs before translation (its an upstream process). I think in the process Rachel is describing, there must be some closer association with the translation machinery and a direct role in translation? is that correct?

The figure Racheal links to clearly shows the direct repression mechanism. I understand that this doesn't always happen, but we need a term for it. I'd still like to make clear that this is direct.

How about:

miRNA mediated inhibition of translation OR direct, miRNA-mediated repression of translation

ValWood commented 9 years ago

The argument comes down to whether regulation of levels of a substrate/intermediate is a type of regulation , so I don't think you objections apply.

I think e presence of a substrate can be regulatory, if it is affecting the process, but not the absence (at least in this case). Would you say that the transcriptional repressor of a subset of genes was negatively regulating translation? That would be the same thing....Intuitively, it feels wrong...but personally I still think that the GO definition of 'biological regulation' is way broader than a biologist's view of regulation....Regulation seems to be used interchangeably with 'affects'.

For this I think any of the solutions above would work...

rachhuntley commented 9 years ago

I would vote for 'miRNA mediated inhibition of translation' as I think including direct in the term name is a bit confusing.

As for the definition "The process in which microRNAs (miRNAs) block the translation of target mRNAs into proteins. Once incorporated into a RNA-induced silencing complex (RISC), a miRNA will typically repress translation if the miRNA imperfectly base-pairs with the 3' untranslated regions of target mRNAs."

"a miRNA will typically repress translation" - the miRNA is not repressing the translation but the other factors that are recruited, so how about changing this to "Once incorporated into a RNA-induced silencing complex (RISC), a miRNA will typically mediate repression of translation if the miRNA imperfectly base-pairs with the 3' untranslated regions of target mRNAs"?

dosumis commented 9 years ago

Done.

dosumis commented 9 years ago

Name and def changed. Leaving open pending addition of more axioms, which require importing missing relations & SO terms.

rachhuntley commented 9 years ago

Great, thanks!

rachhuntley commented 9 years ago

HI David, Was this change made live, as I can't see the name change yet in QuickGO - or were you waiting for the missing relation and SO term imports you mentioned? Thanks, Rachael.

dosumis commented 9 years ago

Sorry, the edit is languishing in my branch. Held off merging becuase of problems with release earlier this week. Will merge back edits and commit them this afternoon. Should be visible tomorrow or day after.

On Wed, Nov 18, 2015 at 11:20 AM, rachhuntley notifications@github.com wrote:

HI David, Was this change made live, as I can't see the name change yet in QuickGO - or were you waiting for the missing relation and SO term imports you mentioned? Thanks, Rachael.

— Reply to this email directly or view it on GitHub https://github.com/geneontology/go-ontology/issues/12155#issuecomment-157682641 .

rachhuntley commented 9 years ago

No problem, thanks.

dosumis commented 9 years ago

Merge, commit & build all worked fine. Will be in tonights' release.

rachhuntley commented 8 years ago

HI David,

I've just noticed a typo in the term name "miRNA mediated inhition of translation". Could you please fix?

Thanks, Rachael.

dosumis commented 8 years ago

Fixed,

dosumis commented 8 years ago

Imported miRNA term from SO and axiomatised most classes referencing miRNA using it.

rachhuntley commented 7 years ago

Sorry to re-open this, but I've only just noticed that "gene silencing by miRNA" is_a "negative regulation of translation". I thought from the discussion above that we decided not to do this? (see from Val's comment on 10th Nov 2015). The child term of gene silencing by miRNA, "miRNA mediated inhibition of translation", is_a "negative regulation of translation, ncRNA-mediated" (see attachment), so I don't think there should be another link to neg. reg. translation through gene silencing by miRNA.

regtranslation

pgaudet commented 6 years ago

Removed parent.