NTR: [transcription pausing by RNA polymerase II]

[sylvainpoux]

Hi GO,

• While working on eralry steps of transcription, I realzed that there is not term for transcription pausing by RNA polymerase II, a step that is now recognized as an integral part of transcription. I will then reannotate the DSIF and NELF complexes, that are currently curated as inhibitors of transcription elongation, which is not exact, since they preceed transcription elongation. This step is also essential for RNA polymerase II transcription elongation surveillance (see ticket NTR: [RNA polymerase II transcription elongation surveillance] #29516)

Thanks

Sylvain

Term: transcription pausing by RNA polymerase II
Definition: A transcription halt following transcription initiation but prior to elongation, during which RNA polymerase II pauses approximately 20-60 nucleotides downstream of the transcriptional start site before proceeding into productive elongation.
Synonym: Promoter proximal pausing by RNA polymerase II
Child of GO:0006366 transcription by RNA polymerase II
PMID:35816930
PMID:33271312

We should also change the definition of transcription elongation
GO:0006368 transcription elongation by RNA polymerase II
FROM:
The extension of an RNA molecule after transcription initiation and promoter clearance at an RNA polymerase II promoter by the addition of ribonucleotides catalyzed by RNA polymerase II.
TO:
The extension of an RNA molecule after transcription pausing and promoter clearance at an RNA polymerase II promoter by the addition of ribonucleotides catalyzed by RNA polymerase II.

[ValWood]

perhaps the term label, if the term is added should be more specific, since transcriptional pausing by RNA polymerase II occurs in other contexts? (i.e termination)

[ValWood]

i.e use proposed exact synonym
promoter-proximal pausing by RNA polymerase II

Is the pause itself a process (I don't know)

NELF and DSIF prevent Pol II from entering productive elongation until phosphorylation by P-TEFb relieves the pause.

but these factors are involved in transcription elongation, so really is the way to capture this is that P-TEFb is involved in "positive/negative regulation of transcription elongation"? because until that signal ( to signify capping is complete, plus presumably an additional signal via the CTD code) elongation does not occur.

My favourite paper on this (I'm biased)
https://www.pombase.org/reference/PMID:19328067

In fact, the activatory/inhibitory mechanism is exactly the same for pausing at termination sites (controlled by P-TEFb (cdk9 in pombe) phosphorylating spt6
https://www.pombase.org/reference/PMID:29899453

I would wait for input from @pgaudet and @colinlog before adding. But it seems that the pausing is really controlled by the phosphorylation/dephosphorylation events controlled by the RNA polymerase II CTD-code mediated signalling.

[sylvainpoux]

Hi @ValWood
Yes, transcription pausing is now considered as a real process. This step acts as a quality control to check (1) if the elongation can take place or if (2) premature transcription termination of transcripts that are unfavorably configured should take place.

[ValWood]

it seems that the process that the pausing is related is a "checkpoint" between initiation and either elongation or surveillance. This would normally be modelled as a type of regulation.

[sylvainpoux]

Hi @ValWood
I see your point but the thing is that some protein complexes, such as DSIF act both during the transcription-pausing (they are a keymediator of this process) and also act as activator of transcription elongation. If we don't create a real term for transcription-pausing, it will be very confusing to have DSIF components that are both positive and negative regulator of transcription elongation. Moreover, we already have many GO terms for checkpoints.
That said, I agree that we should wait for @pgaudet and @colinlog
Sylvain

[ValWood]

I think you are correct, the process should exist in some way, but I wonder how it should be modelled? that's the tricky part. @pgaudet and @colinlog will have a better idea, I'm sure.