Transcription 2018 - 2018-03-15 meeting: review BP terms

From GO Wiki
Jump to navigation Jump to search

Objective

In the BP aspect of the ontology, transcription is classified in two axes:

  • by the promoter/polymerase responsible for the transcription
  • by the transcript type (mRNA, etc).

However both the ontology and the annotations are inconsistent:

  • Not all transcript types have a process
  • Not all transcript types have a regulation of transcription

There is a proposal here as to how to merge terms so that the main axis of classification is the biological output (ie, the transcript type); and secondary, the polymerase, for cases for which more than one polymerase is known to transcribe a specific product https://docs.google.com/spreadsheets/d/1UMwBT4pAJBqUHXYTG2K1bL60ok6QkWPJ3yVFX29nGRQ/edit#gid=0

The first task for the groups is to review a sample of the existing annotations to see if that proposal could be implemented and support accurate annotation, as well as to look at the latest techniques in the field to also ensure that the newer literature is covered in the new structure of the ontology we will propose.


Review BP: miRNA transcription

Ruth


Two key findings

In summary there seems to be growing evidence for pri-microRNA transcription by RNA pol III as well as by Pol II

  1. PMID: 21607569 (2011) Introduction statement: Most of the miRNA genes, which are located predominantly in introns of protein coding genes and intergenic regions, are transcribed by RNA polymerase II (Pol II) [11, 12], and some are transcribed by RNA polymerase III (Pol III) [13] (Fig. 1).
    1. Ref 13 from above is: PMID: 17099701 RNA polymerase III transcribes human microRNAs.https://www.ncbi.nlm.nih.gov/pubmed/?term=17099701
  2. In PubMed there are over 400 papers listed with the search RNA polymerase III microRNAs.
  3. https://www.ncbi.nlm.nih.gov/pubmed/29136251 (2018) authors suggests they have the first comprehensive evidence for RNA polymerase III mediated transcription of microRNAs (the miRs looked at here are all associated with Alu repeats which are apparently transcribed by Pol III).

The other task I was supposed to do was looking for evidence that papers are confirming Pol II is responsible for transcription. I decided just to check the papers that have already been annotated rather than looking at papers not yet annotated.

  1. Looking at a selection of papers annotated to the pri-miRNA transcription and child terms, it seems that in the majority of cases there is no evidence confirming the RNA polymerase involved, and no mention of RNA polymerase II (7 no mention; 1 evidence for RNA pol II; 2 mention of RNA pol II but no evidence).
  2. One paper I have looked at so far mentions RNA Pol II: PMID:18548003 (2008), but this paper demonstrates RNA polymerase II not involved with this statement in results: Likewise, BMP4-mediated induction of both pre-miR-21 and mature miR-21 was resistant to inhibition of RNA polymerase II by α-amanitin, whereas induction of the BMP4 transcriptional target gene ID1 (ref. 30) was abolished (Rachael has confirmed that the data shows BMP signaling regulates miR processing).
  3. https://www.ncbi.nlm.nih.gov/pubmed/?term=21441434%5Buid%5D Arabidopsis paper (2011); anti-Pol II ChIP used to confirm miRNA transcription regulated by increasing Pol II occupancy at miRNA TSS.
  4. I have only looked at 10 of the 38 papers that have been annotated to pri-miRNA transcription and child terms

I would there suggest that the term GO:0061614 pri-miRNA transcription by RNA polymerase II needs a more general parent pri-miRNA transcription, and a more specific child term pri-miRNA transcription by RNA polymerase III. Or that we just have the BP term: pri-miRNA transcription

RNA polymerase studied with ChIP

Astrid

I did a quick search for papers on RNA polymerase studied with ChIP and see indeed there are many. I have no in depth analysis of these papers, but below just one example of a review paper (PMID: 21540878) summarizing what can be learned about RNA pol III transcription from ChIP based analyses



Nat Rev Genet. 2011 May 4;12(7):459-63. doi: 10.1038/nrg3001. Transcription by RNA polymerase III: more complex than we thought. White RJ. RNA polymerase (Pol) III is highly specialized for the production of short non-coding RNAs. Once considered to be under relatively simple controls, recent studies using chromatin immunoprecipitation followed by sequencing (ChIP-seq) have revealed unexpected levels of complexity for Pol III regulation, including substantial cell-type selectivity and intriguing overlap with Pol II transcription. Here I describe these novel insights and consider their implications and the questions that remain.


Review BP: mRNA transcription and RNA poly II transcription

Pascale https://docs.google.com/spreadsheets/d/1Fb6iaIzrQIGFzpulBixDPC6GESCWHZYKrUoezUomF58/edit?usp=sharing

Causal Tab https://docs.google.com/document/d/12rlabGGSBt8JWlfSqnhPUSYPFaZOltznK0c8E7fJifM/

Notes from discussion

  • Many types of RNA are transcribed by different polymerases; however annotations are usually made to a specific term, without the information necessarily being available in the paper.
  • Astrid: 'Regulation of transcription', occurs downstream from all ligands, signaling molecules, etc, and in this sense these annotations are meaningless
  • Ruth: some ligands have other downstream effects, such as transport, regulation of microRNA processing, etc
  • Pascale: regulation of gene expression may be more accurate for ligands etc ?
  • Astrid: important aspects about the mechanisms by which transcription is regulated: for eg the relations that causal-tab is using: regulation by regulating mRNA level, production, mRNA stability, protein production, protein stability, etc.
  • Astrid: target is also essential information
  • Ruth: WRT signaling:
    • signaling pathway involved in regulating tx
    • signaling pathway involved in regulating transport
    • etc
    • This allows to include targets; otherwise if we use extensions to 'regulation of transcription', then we cannot capture the mechanism AND the target

Next tasks