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Source ontology files for the Gene Ontology
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D&T help need for regulation term/transcription/translation #4998

Closed gocentral closed 9 years ago

gocentral commented 16 years ago

How would we deal with this one? I don't know where to start!

It is a regulation of protein expression via upregulation of a translationally silent transcript.

Would it be silly to have a term like:

ntr: negative regulation of gene expression by positive regulation of gene-specific transcription (OR sterol regulatory element binding protein target gene-specific transcription )

as a child of both

GO:0043193 positive regulation of gene-specific transcription or even GO:0035104 positive regulation of sterol regulatory element binding protein target gene transcription

and

ntr: negative regulation of gene expression

Abstract Eukaryotic cells respond to changes in environmental oxygen supply by increasing transcription and subsequent translation of gene products required for adaptation to low oxygen. In fission yeast, the ortholog of mammalian sterol regulatory element binding protein (SREBP), called Sre1, activates low-oxygen gene expression and is essential for anaerobic growth. Previous studies in multiple organisms indicate that SREBP transcription factors function as positive regulators of gene expression by increasing transcription. Here, we describe a unique mechanism by which activation of Sre1-dependent transcription downregulates protein expression under low oxygen. Paradoxically, Sre1 inhibits expression of tco1(+) gene product by activating its transcription. Under low oxygen, Sre1 directs transcription of tco1(+) from an alternate, upstream promoter and inhibits expression of the normoxic tco1(+) transcript. The resulting low-oxygen transcript contains an additional 751 nt in the 5' untranslated region that is predicted to form a stable, complex secondary structure. Interestingly, polysome profile experiments revealed that this new longer transcript is translationally silent, leading to a decrease in Tco1 protein expression under low oxygen. Together, these results describe a new mechanism for oxygen-dependent control of gene expression and provide an example of negative regulation of protein expression by an SREBP homolog.

PMID: 18276645 Nucleic Acids Res. 2008 Apr;36(6):2024-31. Epub 2008 Feb 14.

Reported by: ValWood

Original Ticket: "geneontology/ontology-requests/5014":https://sourceforge.net/p/geneontology/ontology-requests/5014

gocentral commented 16 years ago

Logged In: YES user_id=473890 Originator: NO

Hmmm, to me it seems that the role of Sre1 is in usage of an alternate transcription start site. Many, if not most, genes have multiple start sites and there are many well characterized examples where regulation of start site usage has regulatory consequences. In taking a look at the current process ontology, I don't see any terms for anything relating to regulation of transcription start site usage. I think we definitely need to represent this in GO, perhaps like this:

- regulation of transcription ; GO:0045449 -- regulation of transcription start site selection ; GO:new

Named like that, it seems hard to make child pos and neg terms, since named like this it could be inclusive of cases where usage of one start site goes up while another goes down, so maybe there are better names for the new term, maybe this:

-- regulation of alternate transcription start site selection ; GO:new

With this name, one is definitely designating a 'normal' versus 'alternate' start site, but it would be easier to make pos and neg child terms, since it would be clear that the pos or neg reg was for usage of the alternate start site.

You've also requested a ntr for 'neg reg of gene exp'. Regarding terms with direct relationships to pos and neg regulation of gene expression, I'm not completely sure whether this is warranted, but thinking it through with the possible alternate txn start site term, it might come out like this:

- regulation of gene expression ; GO:0010468 -- negative regulation of gene expression ; GO:new -- negative regulation of gene expression by regulation of alternate transcription start site selection ; GO:new

I'm not completely sure if this is a good way to go. Sometimes alternate start site selection produces a different product, rather than something as simple as up or down reg.

-Karen

P.S. At the moment, I'm not really sure whether the new term should have any additional relationships to either "transcription initiation" or to "transcriptional preinitiation complex assembly", but that could be added later, if appropriate.

Original comment by: krchristie

gocentral commented 16 years ago

Logged In: YES user_id=436423 Originator: NO

Karen - thanks for commenting. Do you want to add this item to the transcription pile, or should we give it to David & Tanya as part of the regulation work?

m

Original comment by: mah11

gocentral commented 16 years ago

Original comment by: tberardini

gocentral commented 16 years ago

Logged In: YES user_id=473890 Originator: NO

Hi,

I see Tanya's just claimed this, which is fine since what I was going to say in response to Midori's question is that I don't think that the addition of at least a basic term for this needs to wait for the txn reorg. While I'm doing that, I can see if I think any additional parentage is appropriate.

-Karen

Original comment by: krchristie

gocentral commented 16 years ago

Logged In: YES user_id=579762 Originator: NO

Thanks for your input, Karen.

Tanya

Original comment by: tberardini

gocentral commented 16 years ago

Logged In: YES user_id=631592 Originator: NO

We think that based on the abstract above, there are actually different processes going on here and more than one annotation could be made. We think there is a need for a term like'transcription start site selection' that would be a child of 'regulation of transcription' and Sre-1 could be annotated to this. It could also be annotated to negative regulation of gene expression, eventually capturing the tco1(+) as the target.

In this case, the Sre-1 gene product is not regulating translation, it is creating a transcript that cannot be translated due to secondary structure. If you could capture the alternate transcript of the tco1(+) gene, then that could be annotated to 'negative regulation of translation'.

Do you want us to add 'transcription start site selection' and 'negative regulation of gene expression'? If we add these two terms, can we consider this closed?

D & T

Original comment by: ukemi

gocentral commented 16 years ago

Logged In: YES user_id=516865 Originator: YES

Yes this would work for me.It struck me afterwards that I needed to create a feature for the alternative transcript and annotate this. I can also capture tco1 as the target of Sre1 for this annotation.

Thnaks.

Val

Original comment by: ValWood

gocentral commented 16 years ago

Logged In: YES user_id=516865 Originator: YES

is this one done?

Val

Original comment by: ValWood

gocentral commented 16 years ago

Logged In: YES user_id=631592 Originator: NO

added GO:0010628 ; positive regulation of gene expression GO:0010629 ; negative regulation of gene expression GO:0010630 ; Regulation of transcription, start site selection

Added correct parantage of existing terms to the + and - regulation terms.

Original comment by: ukemi

gocentral commented 16 years ago

Original comment by: ukemi

gocentral commented 13 years ago

Original comment by: mah11