MP:GO:0046540 U4/U6 x U5 tri-snRNP complex

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GO:0046540 U4/U6 x U5 tri-snRNP complex/GO:0097525 spliceosomal snRNP complex

does not have the parent GO:0005681 spliceosomal complex

val

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/10981

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Ticket moved from /p/geneontology/annotation-issues/1203/

Original comment by: mah11

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• labels: --> parent relationship
• Group: UniProt --> PomBase

Original comment by: mah11

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• assigned_to: Jane Lomax

Original comment by: jl242

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Hi Val,

The term "spliceosomal complex" is meant to be for the series of complexes that are considered to be part of "the" spliceosome, i.e. the series of complexes that form on the mRNA and splice it.

The "U4/U6 x U5 tri-snRNP complex" is a complex that exists as a free complex separate from the mRNA. It becomes part of the spliceosome when it joins the U1 and U2 snRNPs already on the mRNA.

Anyway, as we've currently defined the "spliceosomal complex" term, the "U4/U6 snRNP" and the "U4/U6.U5 snRNP" (and the corresponding U4atac/U6atac terms) are not supposed to have "spliceosomal complex" as a parent.

-Karen

Original comment by: krchristie

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Hi Karen

That isn't what the definition of 'spliceosomal complex' says though:

"Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the splicing of a messenger RNA primary transcript to excise an intron."

Doesn't mention any requirement for the complex to be formed on the mRNA?

I agree with Val - it's very odd for a class like 'spliceosomal snRNP complex' not to have any relationship to 'spliceosomal complex'.

These terms really need formal definitions, I think that would make things a lot clearer. How would you formally define 'spliceosomal complex':

'ribonucleoprotein complex' and capable_of_part_of some 'mRNA splicing, via spliceosome'?

Or is there some implicit temporal aspect here as well to do with when the complexes are formed?

Jane

Original comment by: jl242

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Hi Jane,

Let me start off by satying that my comments are based on my understanding at the time that I worked on these terms before many years ago, with help from Midori for ontology aspects. I don't have time to do research to see if things have changed since then.

I do see looking back that the definition of "spliceosomal complex" doesn't really specify that it needs to be part of the cycle of the assembly of "the spliceosome". This is a tricky one though. At one point in time, people talked about "the spliceosome". However, once people started to understand how splicing works, it becomes very hard to say exactly what "the spliceosome" is because the most common view is that there is a sequential assembly process, and in addition, there are changes in the structure, and possibly also the subunit composition between the 1st and 2nd catalytic reactions. Thus, the "thing" that is referred to in the literature as "the spliceosome" appears to actually represent a cycle of complex assembly (onto a pre-mRNA) and diassasembly (from the spliced mRNA). There was also an idea that there was a penta-snRNP that was a pre-assembeled spliceosome without the pre-RNA, but I think the field was starting to think that this represented a purification artifact due to very mild purification conditions.

At the time I worked on this, the sequential assembly pathway was the majority pathway and that is what I based the ontology terms on, with assistance from Midori. With that context in mind, Midori and I selected the name "spliceosomal complex" to represent the collection of complexes directly on the assembly/disassembly pathway of the complexes that do the catalytic reactions.

The term "U4/U6 x U5 tri-snRNP complex" (GO:0046540) represents a complex that forms separately from "the spliceosome", and then, at a specific part of spliceosomal assembly, joins with the U1 and U2 snRNPs already bound to the pre-mRNA, but the literature at the time definitely did not consider this complex to be part of "the spliceosome", but rather to be a "free" complex similar to the individual U5 snRNP and other individual free snRNPs. The parent term "spliceosomal snRNP complex" (GO:0097525) was created specifically to make a parent term to place these spliceosomal related complexes together to distinguish them from other snRNPs with no relationship to "the spliceosome". Looking now though, from the existing definition, I don't see why the individual free snRNPs, e.g. U5 snRNP are not also children of this term.

So, regarding your suggested formal definition:

'ribonucleoprotein complex' and capable_of_part_of some 'mRNA splicing, via spliceosome'?

a possible problem might be that only some of the child terms (representing complexes in the cycle of assembly/dissambly) are catalytic. Perhaps that is what the "part_of" within the complex relationship "capable_of_part_of" is meant to designate. So, if saying "capable_of_part_of" is appropriate for complexes like the "prespliceosome" (GO:0071010), the "post-spliceosomal complex" (GO:0071020), and other complexes which are not catalytic, then your suggested definition would be fine.

-Karen

Original comment by: krchristie

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• assigned_to: Jane Lomax --> Tanya Berardini

Original comment by: jl242

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Help! I inherited this issue from Jane. From reading the discussion, it sounds like I should do this.

1. make new relationship

GO:0005681 spliceosomal complex --NEW[i] GO:0097525 spliceosomal snRNP complex

1. don't make the formal definition of

'spliceosomal complex' = 'ribonucleoprotein complex' and capable_of_part_of some 'mRNA splicing, via spliceosome'

because some of the child complexes, after the new relationship has been added will not be capable of part of splicing.

Would that be accurate?

Original comment by: tberardini

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HI Tanya,

A. I don't agree about making this relationship:

GO:0005681 spliceosomal complex --NEW[i] GO:0097525 spliceosomal snRNP complex

I don't think that the tri-snRNP should be classified as a "spliceosomal complex". This term is meant to cover the series of complexes that start forming on the pre-mRNA and that convert that pre-mRNA into a spliced RNA (not necessarily the final mRNA in the case of a multi-intron transcript) and a lariat-structure intron, i.e. the series of complexes that are referred to generally as "the spliceosome" and which are shown directly in the circle of complexes in standard diagrams of splicing.

The tri-snRNP is not part of "the spliceosome". Rather it is like the other "free" snRNP complexes that exist as snRNP complexes before they join the pre-mRNA, or subsequent splicing intermediate, to become part of "the spliceosome".

Perhaps the definition of "spliceosomal complex" needs refinement to better describe what is intended as the phrase "and are formed sequentially during the splicing" doesn't seem to be sufficiently meaningful to convey what is intended.

B. I do see an oddity with the term "GO:0097525 - spliceosomal snRNP complex" though. It has only one child: "GO:0097526 - spliceosomal tri-snRNP complex", so GO:0097525 doesn't seem to add any value over just the more specific GO:0097526. Also, based on the name spliceosomal snRNP complex, I would expect it to have all the other snRNP complexes that become part of the spliceosome, e.g. U1 snRNP, U2 snRNP, U4/U6 snRNP, etc. However, these other snRNPs are is_a children only of "GO:0030532 - small nuclear ribonucleoprotein complex", a term which is also the parent of a non-spliceosomal snRNP, "U7 snRNP". In contrast, the two child terms of "GO:0097526 - spliceosomal tri-snRNP complex" have additional is_a parentage to "GO:0030532 - small nuclear ribonucleoprotein complex".

Thus, as currently placed in the structure, the term "GO:0097525 - spliceosomal snRNP complex" serves no purpose. If we keep it, I think it should become an additional parent of all of the other "free" snRNPs that become part of "the spliceosome" so that it becomes a grouping term for the variety of snRNPs that have "free" forms when they are not part of "the spliceosome" that distinguishes "spliceosomal" snRNPs from all snRNPs, not all of which are part of the spliceosome. If we don't want that kind of grouping term, I think we should consider obsoleting it.

1. Then regarding Jane's proposed formal definition:

'spliceosomal complex' = --'ribonucleoprotein complex' -- and capable_of_part_of some 'mRNA splicing, via spliceosome'

I am rethinking this. My initial hesitation about this was that there are only two complexes along the cycle that have catalytic activity, but possessing catalytic activity may be too narrow of an interpretation of what constitutes being "capable_of_part_of some 'mRNA splicing, via spliceosome'".

If we consider

• the various binding steps which recognize the key sequences in the pre-mRNA,
• the conformational rearrangements to place those key sequences adjacent to each other, - the conformational rearrangements to release the spliced RNA, the excised lariat, and the constituent snRNPs as well as the non-RNA-containing Prp19 protein complex

as part of splicing via the spliceosome, then I think Jane's definition is accurate.

-Karen

Original comment by: krchristie

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One more try:

1. Refine the definition of "spliceosomal complex" to better describe what is intended by the phrase "and are formed sequentially during the splicing". No new relationship to GO:0097525 spliceosomal snRNP complex.

From: Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the splicing of a messenger RNA primary transcript to excise an intron.

To: Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during and contribute to the splicing of a messenger RNA primary transcript to excise an intron.

I think this is broad enough to cover binding/recognition functions of a spliceosomal complex as well as actual catalytic activity. This will also allow us to add the logical definition.

1. 'spliceosomal complex' = --'ribonucleoprotein complex' -- and capable_of_part_of some 'mRNA splicing, via spliceosome'
2. Do something with "GO:0097525 - spliceosomal snRNP complex" . Add children as suggested by Karen (which ones are the free snRNPs?) or obsolete. Preferences?

Original comment by: tberardini

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Hi Tanya,

=> Refining the definition of "spliceosomal complex"

I wonder if this very slight modification:

From: Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the splicing of a messenger RNA primary transcript to excise an intron.

To: Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during and contribute to the splicing of a messenger RNA primary transcript to excise an intron.

does enough to clarify the intent because one could argue that the various free snRNPs, including the U4/U6.U5 tri-snRNP that started this thread also "contribute to" the splicing. Earlier in this thread, in response to my comment about the intent, this was Jane's response:

"Doesn't mention any requirement for the complex to be formed on the mRNA?"

So, I am wondering if we should be more explicit about the the inclusion of the substrate RNA as part of the complex. Note that we shouldn't call it the mRNA because the spliceosome also splices some snoRNAs, like U3, and performs trans-splicing in some species. So, here's an attempt:

To: Any of a series of ribonucleoprotein complexes that contain snRNA(s) and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the spliceosomal splicing of one or more substrate RNAs, and which also contain the RNA substrate(s) from the initial target RNAs of splicing, the splicing intermediate RNA(s), to the final RNA products. During cis-splicing, the initial target RNA is a single, contiguous RNA transcript, whether mRNA, snoRNA, etc., and the released products are a spliced RNA and an excised intron, generally as a lariat structure. During trans-splicing, there are two initial substrate RNAs, the spliced leader RNA and a pre-mRNA.

=> logical definition - I'm glad you agree that we can include the binding/recognition functions. That should help distinguish the "spliceosomal complex" from the "spliceosomal snRNPs"

=> Do something with "GO:0097525 - spliceosomal snRNP complex"

If we decide to keep "GO:0097525 - spliceosomal snRNP complex", this is what I think we should do.

A. Change its is_a parent from: GO:0030529 - ribonucleoprotein complex to: GO:0030532 - small nuclear ribonucleoprotein complex

B. Move all child terms of "GO:0030532 - small nuclear ribonucleoprotein complex" EXCEPT "GO:0005683 - U7 snRNP" to be direct child terms of "GO:0097525 - spliceosomal snRNP complex" instead.

With the proposed change in parentage of "GO:0097525 - spliceosomal snRNP complex", the terms like "U1 snRNP" will still under "GO:0030532 - small nuclear ribonucleoprotein complex"

Original comment by: krchristie

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Thanks for your comments, Karen. Very helpful. I'll leave this open a little longer in case others want to add anything else.

Original comment by: tberardini

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• status: open --> closed-fixed

Original comment by: tberardini

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Done as described in last comment from Karen except I made the logical definition be like this:

+intersection_of: GO:0030529 ! ribonucleoprotein complex +intersection_of: capable_of_part_of GO:0008380 ! RNA splicing

instead of

+intersection_of: GO:0030529 ! ribonucleoprotein complex +intersection_of: capable_of_part_of GO:xxxx ! 'mRNA splicing, via spliceosome'

because the definition refers to more than just mRNA splicing.

Closing now.

Thanks, everyone, for your input.

Original comment by: tberardini

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Hey Tanya,

I see your point about "because the definition refers to more than just mRNA splicing".

However, because we're talking specifically about the "spliceosomal complex", I think the better solution would be to fix the fact that all the spliceosomal splicing terms specify "mRNA" instead of just "RNA". I suspect I didn't know that spliceosomes also splice some snoRNAs at that time, so we thought we could narrow it to mRNA.

This logical definition:
+intersection_of: GO:0030529 ! ribonucleoprotein complex +intersection_of: capable_of_part_of GO:0008380 ! RNA splicing is probably true for other kinds of splicing, not just for this term.

-Karen

Original comment by: krchristie

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I'm going to remove the logical definition. It's Friday and this issue needs to stay closed. :)

Original comment by: tberardini

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It's gone.

-intersection_of: GO:0030529 ! ribonucleoprotein complex -intersection_of: capable_of_part_of GO:0008380 ! RNA splicing

Original comment by: tberardini