NTR: [nuclear-transcribed mRNA decay via premature transcription termination ] PMID:34352089

[ValWood]

• Suggested term label:

GO:NEW. nuclear-transcribed mRNA decay via premature transcription termination 


• Definition (free text)

A negative regulation of gene expression that operates via a degradation pathway dependent on premature termination of transcription to generate cryptic unprotected transcripts. The pathway operates via a poly(A)-independent mechanism where co-transcriptional cleavage of nascent transcripts by S. Pombe Pac1 endonuclease ( human DROSHA) and creates an entry point for the 5′-3′ exonuclease Dhp1 (human XRN2) complex, leading to premature RNAPII termination and degradation.


• Reference, in format PMID:#######

PMID:34352089

• Gene product name and ID to be annotated to this term

See definition.

• Parent term(s)

part_of GO:0000294 nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay is_a GO:0006369 termination of RNA polymerase II transcription

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

none

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

Synonym: torpedo dependent termination (exact) 
Synonym: Pac1-dependent co-transcriptional cleavage (exact)
 Synonym: termination of RNA polymerase II transcription, poly(A)-independent (related)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

• I am wondering if this new suggested them is the same as GO:0030847 termination of RNA polymerase II transcription, exosome-dependent because this has the exact syonym transcription termination from Pol II promoter, poly(A)-independent and the exosome-dependency implies some link to degradation of cryptic transcripts.

however the definition is The process in which transcription of nonpolyadenylated RNA polymerase II transcripts is terminated; coupled to the maturation of the RNA 3'-end.

and the term I have requested is not coupled to 'maturation' which implies a functional transcript (although the same gene product does seem to have a role in maturation via other pathways). The point of this pathway is that the transcribing mRNAs are prematurely termination, not polyadenylated and therefore shunted into the degradation pathway, so the 'end processing' here is not maturation.

• requested in consulation with the author https://curation.pombase.org/pombe/curs/f5403fffd3ecaf81/ro

[ValWood]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472303/ I think they might be the same thing. However the term should refer to 3' end processing, NOT maturation. If this does turn out to be the case I would obsolete the GO:0030847 is badly defined, AND the exosome is the terminal step in multiple unrelated degradation pathways so it isn't helpful to have an 'exosome-dependent' term

[pgaudet]

This is a weird branch - are these real processes? Sound like MFs in BPs, at least the term labels, and to some extent the definitions - ie 'a pathway that starts with an endo/exonuclease reaction:

• GO:0000294 nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay
• GO:0043927 exonucleolytic nuclear-transcribed mRNA catabolic process involved in endonucleolytic cleavage-dependent decay ?

Should this new term somehow be under GO:0071028 nuclear mRNA surveillance?

[ValWood]

This area is a bit mixed up. But I think that is partly to do with how the community distinguish the pathways. They use the nucleases to label the pathway. That said I think there could be some rationalization, because there does seem to be some redundancy. I could ask Juan Mata (PomBase PI who works a lot on RNA processing) if he could provide expertise to help to consolidate the existing pathways with the newly emerging information when you are ready to address them.

The new term is a GO:0071028 nuclear mRNA surveillance pathway

[pgaudet]

There is also 'GO:0030847 termination of RNA polymerase II transcription, exosome-dependent', which seems to descibe a similar process, at least if we go by the papers annotated to this term.

[ValWood]

This term was to describe the torpedo model. ~I don't think it is exosome dependent but I'm not sure~

@colinlog has mentioned this a couple of times because it is a mechanism for regulating gene expression.

I was waiting for more papers on the pathway in order to describe it more precisely.

You might be right because the paper I used for GO:0030847 says These findings uncover a mechanism of cotranscriptional RNA surveillance whereby termination of transcription by the exosome prevents formation of aberrant readthrough RNAs and transcriptional interference at neighboring genes.

[colinlog]

This paper is very nice for the torpedo model, I believe PMID:31805520