inc parent: srb mediator

[gocentral]

srb mediator should not be a child of mediator (or holoenzyme)

should probably be a sibling of haloenzyme

(binding of srb-mediator with mediator is mutually exclusive of mediator being part of halo).

Karen, was that correct...I left the papers in Daves lab...

(perhaps change name term to Srb-mediator subcomplex?)

not sure...

needs looking at anyway

Reported by: ValWood

Original Ticket: "geneontology/ontology-requests/1802":https://sourceforge.net/p/geneontology/ontology-requests/1802

[gocentral]

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Hi Val - the literature for this is really confusing - have you got a good paper

Original comment by: jl242

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[from Claes Gustafsson]

Hi Val, Mediator exists in two forms:

1. Core Mediator

2. Srb8-11/Mediator

This is true in both yeast and metazoan cells. The core Mediator may associate with RNA polymerase II to form a holoenyzme. In contrast, the Srb8-11/Mediator can not interact with pol II. The difference between these two complexes is the Srb8, Srb9, Srb10, and Srb11 subunits, which forms a specific module (the Srb8-11 module). Mediator interactions with pol II and the Srb8-11 module are mutually exclusive! (ref: Samuelsen CO, Baraznenok V, Khorosjutina O, Spahr > H, Kieselbach T, Holmberg S, Gustafsson CM. TRAP230/ARC240 and TRAP240/ARC250 Mediator subunits are functionally conserved through evolution. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6422-7)

In a similar way the human Mediator also exists as a core complex, known under many different names, e.g. CRSP, PC2. There is also a larger form of Mediator containing the mammalian homologues to Srb8-11. This larger form of Mediator also have many different names (e.g. ARC-L, TRAP/SMCC etc.) The human core Mediator may interact with pol II, whereas the Srb8-11 containing Mediator does not.

(ref: Taatjes DJ, Naar AM, Andel F 3rd, Nogales E, Tjian R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science. 2002 Feb 8;295(5557):1058-62., Naar AM, Taatjes DJ, Zhai W, Nogales E, Tjian R. Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev. 2002 Jun 1;16(11):1339-44.

Finally - Mediator and Srb/Mediator are collective terms, which may refer to both the core Mediator and to the Srb8-11/Mediator. The reason why some people use Srb/Mediator instead of just Mediator, is probably to honor the genetic studies done by the R. A. Young laboratory, which identified the SRB genes.

I would also like to recommend a recent paper in Molecular Cell, in which the Mediator field has come together and suggested a unified nomenclature (ref: A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Mol Cell. 2004 Jun 4;14(5):553-7.)

Best regards,

Claes

Original comment by: jl242

[gocentral]

• milestone: --> 224410

Original comment by: jl242

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The current terms are:

DNA-directed RNA polymerase II, holoenzyme ---[p] mediator complex ------[i] Cdc73/Paf1 complex ------[i] Srb-mediator complex

I don't think that the Cdc73/Paf1 complex (which I think should actually now be called the Paf1 or PAF complex) should be a child of mediator complex (see PMID: 15149594) - should probably go straight under DNA-directed RNA polymerase II, holoenzyme.

Original comment by: jl242

[gocentral]

• assigned_to: nobody --> jl242

Original comment by: jl242

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Hi,

This item has been open for a long time. Please comment to let us know whether you would like it to remain assigned to you, or would prefer it to be reassigned. (You don't necessarily have to work on it immediately if you keep it; we just need to know whether it's still on your list.)

Thanks, Midori & David Ontology development group managers

Original comment by: mah11

[gocentral]

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I have received another e-mail about mediator and my annotations not being up to date.

This e-mail also mentions The four subunits Med12, Med13 (formerly Trap240 or Srb9), Cdk8 (formerly Srb10 or Prk1) and cyclin C/cycC (formerly Srb11) belong to a repressive sub-module of the Mediator known as the Cdk8 module. Our group has published two papers on its structure and function that you can link to if you like (Samuelsen et al 2003 PMID 12738880, Elmlund et al 2006 PMID 17043218). The pombe Cdk8 cyclin-dependent kinase was originally described by Watson & Davey (1998, PMID 9559556).

So, I guess we also need a componet term for the repressive sub-module.

I just wondered what the status was of this SF item before I start.

Original comment by: ValWood

[gocentral]

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Val - I'm afraid for me this SF item is lost in the mists of time...if you propose a solution I'd be happy to implement it, but don't have much brainpower to divert to it at the moment I'm afraid...

Original comment by: jl242

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Hi Jane,

Do you want to just unassign this from you? I'll add what I think it should be later today (hopefully) when I have read the papers and I asked Karen C. who would know best to take a look.

Val

Original comment by: ValWood

[gocentral]

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From : The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II Hans Elmlund,Vera Baraznenok,Martin Lindahl,Camilla O. Samuelsen, Philip J. B. Koeck,Steen Holmberg,Hans Hebert, and Claes M. Gustafsson

"The subunit composition of S. cerevisiae Mediator has been studied in detail, and 21 proteins are bona fide members of the core Mediator complex (1, 8, 9). In addition, a subgroup of Srb proteins, Med12/Srb8, Med13/Srb9, Cdk8 (cyclin-dependent kinase 8)/Srb10, and CycC/Srb11, forms a specific module (the Cdk8 module) that is variably present in Mediator preparations (10, 11). The smaller, core Mediator (S Mediator) lacking the Cdk8 module has a stimulatory effect on basal transcription in vitro (5, 12). The larger form of Mediator (L Mediator), containing the Cdk8 module, instead represses basal transcription in vitro, and genetic analysis also indicates that the Cdk8 module is involved in the negative regulation of genes in vivo (13)."

In GO Srb-mediator complex GO:0016592 is A multiprotein transcriptional mediator complex that interacts with the carboxy-terminal domain of the largest subunit of RNA polymerase II and is essential for transcription of most protein-coding genes. The Saccharomyces complex contains a core of core complex consists of 16 polypeptides: Srb2, -4, -5, -6, and -7, Med1, -2, -4, -6, -7, and -8, Gal11, Sin4, Rgr1, Rox3, and Pgd1 proteins; mammalian Srb-mediator complexes include homologs of yeast Srb and Med proteins.

and seems to describe the mediator with srb, but it is a child of mediator complex GO:0000119 A protein complex that enables the RNA polymerase II-general RNA polymerase II transcription factor complex to react to transcriptional activator proteins; also enhances the level of basal transcription.

I don't know how we need to resolve this.

We need a new term for Srb submodule (this seems to be also referred to as Cdk8 module so this should be a synonym.

I'm not sure what the new rules are with respect to complexes terms, but It looks as though

Srb-mediator complex GO:0016592 --mediator core complex (If this is the mediator without Srb) --Srb submodule

would work?

Val

Original comment by: ValWood

[gocentral]

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I am now reading another paper, and it seems like the Srb submodule doesn't necessarily exist on its own?

So the existing terms are OK. The Srb form doesn't associated wtih RNA polymerase II though....so the existing parentage is incorrect.

1. Srb mediator shouldn't be a child of mediator, or RNA polII holoenzyme.

2. Should mediator be a child of RNA pol holoenzyme? (it is now)

3. It seems like Srb mediator and mediator should be siblings

4. We only need the Cdk8 module as a sperate term if this complex is known to exist when not as a part of mediator.

Original comment by: ValWood

[gocentral]

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Hi Val,

This SF item gives more detail about Mediator and the distinction between it and SRB/Mediator than I knew, so without doing some reading, I can't really comment much at the moment. I'm currently involved in finishing up a revision of the process terms for rRNA processing and after that Midori's asked me to take a look at a group of transcription related items.

-Karen

Original comment by: krchristie

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Val - yes, I'll happily unassign this to myself ;)

Original comment by: jl242

[gocentral]

• assigned_to: jl242 --> nobody

Original comment by: jl242

[gocentral]

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OK, Tomas says

As far as we know from studies in pombe, cerevisiae and mammalian cells the Cdk8 module does not exist as an independent complex. That said it appears to dissociate from the core mediator upon association with RNA polymerase. We don't know where the Cdk8 module "goes" during this step in transcriptional initiation but it could perhaps associate with another promoter-bound factor. But in summary, from what we know to date the Cdk8 module does not seem to have a function independent of the core mediator complex. So it would make sense to annotate it within the mediator ontology.

...So I think the existing terms are OK. Just the parentge is wrong.

Srb-mediator complex shouldn't be a child of mediator (they should be siblings)

and lots of synonyms can be added...see below

Original comment by: ValWood

[gocentral]

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Hi Val,

I've dealt with the parentage problem, but I couldn't figure out what synonyms you want added. Can you put a list here? then I'll add 'em.

m

Original comment by: mah11

[gocentral]

• labels: --> Other term-related request
• assigned_to: nobody --> gomidori
• status: open --> open-fixed

Original comment by: mah11

[gocentral]

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The larger form of the mediator Srb-mediator complex is also known as L Mediator and CDK8-containing TRAP/Mediator and the other form (Mediator) is also known as S Mediator

then can close this

Original comment by: ValWood

[gocentral]

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synonyms added. whew! m

Original comment by: mah11

[gocentral]

• status: open-fixed --> closed-fixed

Original comment by: mah11

[gocentral]

• milestone: 224410 --> PomBase

Original comment by: mah11