NTR: priming of CTD phosphorylation

[gocentral]

hyperphosphorylation of RNA polymerase II C-terminal domain has no sibling

add sibling priming phosphorylation of RNA polymerase II C-terminal domain DEF The iniitial phosphorylation of RNA polymerase CTD which preceeds hyperphosphorylation

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/6820

[gocentral]

Hi Karen,

Can you take a quick look at this? I can add the term if no problems, but if it's more complicated than it looks we'll need your input.

thanks, m

Original comment by: mah11

[gocentral]

• assigned_to: nobody --> kchris

Original comment by: mah11

[gocentral]

Hi

I've never heard the term 'priming phosphorylation' for the RNAPII CTD so it seems like an odd choice of a term name and I can't comment on the accuracy of the definition. If there's a reference that uses this terminology, I'll be happy to take a quick look, but I don't see any PMID's provided with the suggested def.

Typically, for the CTD, I've seen the terms hypophosphorylated and hyperphosphorylated and the CTD cycles between these two states. It would probably make sense to have a term to represent the hypophosphorylated state, though the parallel term name "hypophosphorylation of RNA polymerase II C-terminal domain" seems odd to me since this is a dephosphorylation event. "Generation of hypophosphorylated C-terminal domain of RNA polymerase II" seems better. If we go with that, perhaps it would be good to change the term name of the CTD hyperphosphorylation term to be parallel.

Looking at the parentage of the CTD hyperphosphorylation term, do we need the "hyperphosphorylation" term at all. It does not seem to be a general thing since it only has one child. If we do keep it, could it's definition be changed to use the word 'extensive' like in the CTD hyperphos term, instead of "excessive" which seems to imply an abnormal state.

-Karen

Original comment by: krchristie

[gocentral]

Val - looks like you have to cough up a reference ;)

Both - I have no objection to changing the def of the existing hyperphosphorylation term. I think it has its name because that's what we see in the literature, and if it would help, we can add a synonym (exact?) using just plain "phosphorylation". Or maybe Val's papers will make the case for a new term.

Original comment by: mah11

[gocentral]

I think that use of "hyperphosphorylation" with respect to the CTD is completely appropriate. It's used context a lot.

It's just the plain "hyperphosphorylation" (GO:0048151) that I wonder if is needed at all. Also, I've just noticed that it is currently placed as an is_a child of "phosphorylation", but the definition seems inconsistent with that parentage:

Def: The excessive phosphorylation of a protein, as a result of activation of kinases, deactivation of phosphatases, or both.

-Karen

Original comment by: krchristie

[gocentral]

Thanks for clarifying (I overlooked the GO ID for the "hyperphosphorylation" parent); I agree that we don't need GO:0048151, and the CTD term can go directly under phosphorylation.

m

Original comment by: mah11

[gocentral]

I only suggested it because I had captured the information that it was "priming" in free test but I had nowhere to put it so it was just sitting in my log files.

When I looked, tha fact that hyperphosphorylation of RNA polymerase II C-terminal domain had no sibling seemed to justify the addition of this term.

The paper is http://www.ncbi.nlm.nih.gov/pubmed/19328067?dopt=Abstract

Original comment by: ValWood

[gocentral]

OK, having read through the paper Val indicated, and also through a 2006 review (Phatnani & Greenleaf, PMID:17079683) referenced in that paper, I think I would avoid the phrase "priming phosphorylation" unless and until it gains wider usage than one paper. While it's good that they're doing the experiments specifically for the pombe genes, it's not exactly new to see that the Cdk9 equivalent kinase (acts on Ser2's) prefers CTD's that already have Ser5-P (rather than plain Ser5) as a substrate, and I don't see the "priming" terminology in the review from the Greenleaf lab.

So, having had a good read through the Greenleaf (major player in field for many, many years) review, I would suggest these changes:

1. changes to "hyperphosphorylation of RNA polymerase II C-terminal domain" (GO:0016245)

A. Revision to def: While the def I wrote some time ago seems like an accurate reflection of what was known at the time, I think it is not entirely accurate now. I propose removing all or part of some sentences and keeping this as the new definition:

Def: The production of an RNA polymerase II enzyme where the carboxy-terminal domain (CTD) of the largest subunit is extensively phosphorylated. Specific types of phosphorylation within the CTD are usually associated with specific regions of genes, though there are exceptions. The phosphorylation state regulates the association of specific complexes such as the capping enzyme or 3'-RNA processing machinery to the elongating RNA polymerase complex.

B. Revision to parentage: It is not true that all (hyper)phosphorylation of the CTD occurs during initiation so remove the part_of relationship to "transcription initiation from RNA polymerase II promoter" (GO:0006367).

C. Name change from current to "Generation of hyperphosphorylated C-terminal domain of RNA polymerase II"

D. New synonyms:

• Generation of hyperphosphorylated CTD of RNA polymerase II
• Generation of II(0) form of RNA polymerase II

2. Hmmm, wrote all of the above and then noticed this term: "phosphorylation of RNA polymerase II C-terminal domain" (GO:0070816)

I don't think there is really any distinction between the two. When you P a significant number of the serines in the repeat when there are 25 (Sc) to 52 (mammalian) copies of the repeat, you basically get "hyper"P.

So, I think I would use this name: "phosphorylation of RNA polymerase II C-terminal domain" since it is more neutral, and make the "hyperphosphorylation of RNA polymerase II C-terminal domain" name a synonym, as well as the new synonyms I suggested above.

I prefer the position of the current "hyper..." term though since all P on the CTD is regulatory. Is there some logic to determine which GOID is the preferred one to keep when the proposed merge is keeping the name of one but the position of the other?

... and then looking at this def and my revised one above, how 'bout this combined one:

The process of introducing a phosphate group on to an amino acid residue in the C-terminal domain of RNA polymerase II. Typically, this occurs during the transcription cycle and results in production of an RNA polymerase II enzyme where the carboxy-terminal domain (CTD) of the largest subunit is extensively phosphorylated, often referred to as hyperphosphorylated or the II(0) form. Specific types of phosphorylation within the CTD are usually associated with specific regions of genes, though there are exceptions. The phosphorylation state regulates the association of specific complexes such as the capping enzyme or 3'-RNA processing machinery to the elongating RNA polymerase complex.

3. Obsolete "hyperphosphorylation" (GO:0048151) for the reasons discussed earlier in this thread. Midori, you're probably better than I am at phrasing the obsoletion reasons, but let me know if you need any further input from me.

4. New phosphorylation terms

Term: phosphorylation of RNA polymerase II C-terminal domain serine 5 residue Def: The process of introducing a phosphate group onto a serine residue at position 5 within the heptapeptide repeat (YSPTSPS) of the C-terminal domain of RNA polymerase II. Typically, phosphorylation of serine 5 (Ser5) occurs near the 5' ends of genes. It is generally still observed in the middle of genes, overlapping with phosphorylation of serine 2, but is generally not present at the 3' ends of genes. In vivo, Ser5 phosphorylation occurs primarily through the action of TFIIH (KIN28 in S. cerevisiae, CKD7 in metazoans). Def dbxref: PMID:17079683

Term: phosphorylation of RNA polymerase II C-terminal domain serine 2 residues Def: The process of introducing a phosphate group onto a serine residue at position 2 within the heptapeptide repeat (YSPTSPS) of the C-terminal domain of RNA polymerase II. Typically, phosphorylation of serine 2 (Ser2) occurs subsequent to phosphorylation of serine 5 and is thus seen in the middle and 3' ends of genes. In vivo, Ser5 phosphorylation is primarily performed by CTDK-I in S. cerevisiae or CDK9 in metazoans. Def dbxref: PMID:17079683

Both of these terms would get this parentage:

is_a: phosphorylation of RNA polymerase II C-terminal domain (ID = whichever one we keep btw 70816 & 16245)

don't think we'll need any direct parentation to a regulation term since the parent will already have an is_a relationship to "regulation of transcription from RNA polymerase II promoter" (GO:0006357)

5. Changes to "dephosphorylation of RNA polymerase II C-terminal domain" (GO:0070940)

A. Proposed additions to the def to give a little more context

The process of removing a phosphate group from an amino acid residue in the C-terminal domain of RNA polymerase II. Some dephosphorylation occurs during transcription while some may occur after the enzyme is released from the template in order to prepare it for the beginning of the transcription cycle again.

B. Additional parentage

is_a "regulation of transcription from RNA polymerase II promoter" (GO:0006357)

because this is all regulatory too

C. New synonyms

• Generation of hypophosphorylated CTD of RNA polymerase II
• Generation of II(A) form of RNA polymerase II

I've done all this based mainly on the Greenleaf review I cited, though it's certainly consistent with previous things I've read/heard and Greenleaf is definitely a long-time player in this field. But definitely let me know if you think I missed anything or have any other suggestions.

-Karen

Original comment by: krchristie

[gocentral]

oops,

Addendum to 5.A. For the proposed new def of the dephos term, I'd like to add this sentence to the end of what I proposed previously.

RNA polymerase II with little or no phosphorylation is referred to as the hypophosphorylated or II(A) form.

thanks,

-Karen

Original comment by: krchristie

[gocentral]

Hi Karen,

Impressive amount of detail! Everything sounds fine, and there's no way I would know of anything you might have missed (we'll see what Val says).

For ID and merging, we usually go with whichever ID is used for more annotations, or, if there's not a clear difference in usage, the older one (usually these correlate anyway, although this case is an exception). I wouldn't bother changing that approach based on which parentage we keep, so I would use GO:0070816.

I'll compose and send an obsolete-alert email for GO:0048151.

m

Original comment by: mah11

[gocentral]

Hi Midori,

Thanks for doing the obsolete-alert email. I'll wait for Val to comment to procede on the rest of this item, which likely means January since Stanford is on shutdown for the rest of the year. If Val is OK with it all and you'd like to proceed before that, feel free .

thanks,

-Karen

Original comment by: krchristie

[gocentral]

sorry, I though I added a comment to this last week but it didn't appear.

I agree, go ahead.

Val

Original comment by: ValWood

[gocentral]

I've now made GO:0048151 obsolete, since the announced date passed during the break. Karen - I haven't made any of the other changes so far; I'll do the rest if you don't get to it some time this week.

m

Original comment by: mah11

[gocentral]

Changes all done as described -- please check. m

Original comment by: mah11

[gocentral]

• milestone: --> 224410
• assigned_to: kchris --> gomidori
• labels: --> Other term-related request
• status: open --> closed-fixed

Original comment by: mah11

[gocentral]

• milestone: 224410 --> PomBase

Original comment by: mah11