Transcription

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[edit] Background

There are a large number of Source Forge items (some as old as 2003) relating to problems with the representation of transcription, especially in both Molecular Function and in Biological Process. A major goal of this reorganization is to come up with a more sensible and consistent organization of transcription related terms.

Some of the transcription related Source Forge items assigned to me involve more specific issues. I will attempt to address these as well, though perhaps not in the initial phase.

[edit] Source Forge items to be addressed

commencing June 2008, trying to get a handle on the various issues that have been reported

[edit] reverse chronological list

2008-06-21 - transcription factor activity, child problem
2008-05-12 - transcription activator/coactivator
2008-04-28 - mp:specific RNA polymerase II transcription fact
2008-03-21 - NTR: specific transcriptional activator activity
2008-02-12 - transcriptional preinitiation/initiation
2008-02-12 - transcription initiation def
2008-02-04 - mv DNA-directed RNA polymerase II, holoenzyme complex?
2007-12-18 - term merge?nonspecific RNA polymerase
2007-12-18 - missing parent:RNA pol II transcription factor activity
2007-11-14 - rg: def. of holo vs. core TFIIH complex
2007-08-06 - query parent hyperphosphorylation of RNA polymerase II
2007-07-25 - transcription related terms
2007-06-13 - transcription initiation def
2006-11-03 - general and specific transcription
2006-08-16 - update def: transcription factor TFIIIC complex
2006-08-10 - Definition change GO:0030014; CCR4-NOT complex
2006-05-23 - new MF terms for eukaryotic RNA polymerase binding
2006-02-02 - Transcription factor related
2005-10-06 - snoRNA transcription
2004-05-14 - transcription factors
2004-02-02 - promoter escape
2004-02-02 - promoter opening
2003-03-17 - transcription factor activity

[edit] trying to group items that are similar

Here I've gone through all the transcription related items assigned to me and identified which aspect they relate to and summarized the issues in each. Several items were closed as duplicates of other items. When comments were present, they were pasted into the remaining open item.


[edit] Summary of Issues

Many of these issues are derived from the various SourceForge items. However, I am also putting in other things I come across.

[edit] Ontological Issues

[edit] In Function
  1. transcription factor activity
    • poorly defined and placed
    • does not have relationships with things like specific RNA polymerase II trancription factor
    • has DNA binding parentage, while most other things under transcription regulator activity do not
  2. sets of terms that may be equivalent/synonymous
    • negative regulator of basal transcription activity (GO:0017163) and general transcriptional repressor activity (GO:16565)
    • nonspecific RNA polymerase II transcription factor activity (GO:0016252) and general RNA polymerase II transcription factor activity (GO:0016251)
  3. Lots of gene product or complex specific terms, e.g. sigma or RNA polymerase II
    • Do we need to represent things like RNA polymerase II mediator activity with a specific function term?
    Perhaps just general RNA polymerase II transcription factor activity would be sufficient, and the genes would also be annotated to the component term mediator complex?
    • Do we even need to have RNA polymerase I, II, and III factors separately? We don't have different functions for each of these 3 complexes. Perhaps we only want to have terms for the basic function and leave the polymerase specificity to process and component.
  4. requested new RNA polymerase binding terms in function
    How specific do we want to go?
  5. terms with general sounding names but Pol II specific defs
    • transcription cofactor activity GO:0003712
    • transcription coactivator activity GO:0003713
    • transcription corepressor activity GO:0003714
  6. undefined terms
    • cAMP response element binding protein binding GO:0008140
    • ligand-dependent nuclear receptor transcription coactivator activity GO:0030374
    • thyroid hormone receptor coactivator activity GO:0030375
    • transcription initiation factor activity GO:0016986
      Has two child terms (mito init factor and sigma factor), both of which are defined
[edit] In Process
  1. sets of terms that may be equivalent/synonymous
    • positive regulation of transcription from RNA polymerase II promoter (GO:0045944) and positive regulation of transcription from RNA polymerase II promoter, global (GO:0045817) or if regulation of global transcription needs a distinct term, perhaps defs could be clearer
    • tRNA transcription from RNA polymerase III promoter (GO:0042797) and tRNA transcription (GO:0009304) - not sure the more specific term is really needed (right now it's the only child of its parent), unless we're going to go the other way and have mitochondrial tRNA transcription.
  2. inconsistency in term name organization
    • positive regulation of specific transcription from RNA polymerase II promoter (GO:0010552) and positive regulation of transcription from RNA polymerase II promoter, global (GO:0045817) - would be good to have these two term names done in the same way instead of one with a comma and one without
  3. no representation of transcript cleavage, like that stimulated by PPR2, see Weilbaecher RG, et al. (2003) Intrinsic transcript cleavage in yeast RNA polymerase II elongation complexes. J Biol Chem 278(26):24189-99 PMID:12692127, or should this be in function?...

[edit] Biological Questions

  1. General vs specific transcription
    1. Is this distinction specific to Pol II, or does it also apply to Pol I and Pol III (other RNAPs)?
    2. Defining the distinction between general and specific txn?
    3. Defining the distinction between general and specific repressors?
    4. Is nonspecific synonymous with general?
    5. Do specific transcriptional activators need to have DNA binding activity?
  2. the transcription cycle
    1. defining initiation - does initiation include PIC formation?
    2. promoter opening - Is this step regulated/activated for RNAP's other than RNAPII?
    3. promoter escape - part of initiation or elongation?
    4. CTD phosphorylation - part of initiation or elongation?

[edit] Research

start on p 16


List of references relevant to transcription

[edit] Phrases of note

- from Geiduschek EP & Kassavetis GA. (2001)

  • core transcription factors (for Pol III)
  • direct promotor recognition (for Pol III)
  • RNA chain elongation
  • hydrolytic retraction (a form of transcript cleavage)
  • endopyrophosphorolytic retraction (a form of transcript cleavage)
  • holoenzyme - "In the original bacterial terminology, a holoenzyme is the form of the RNA polymerase that is competent to execute an entire transcription cycle, including specific initiation."
  • promoter recognition - primary function of bacterial sigma
  • regulation of promoter clearance - secondary function of sigma70
  • assembly of anti-terminating elongation complexes - secondary function of sigma70

- from Oficjalska-Pham D, et al. (2006)

  • general negative cofactor (for Pol III)


[edit] Transcription cycle

"In bacterial transcription, the functions of core promoter sequence recognition and initiation of promoter opening are combined in one subunit of the RNA polymerase holoenzyme. In eukaryotic and archaeal transcription this labor is divided: core promoter recognition is assigned to the transcription initiation factors. Initiation of promoter opening is largely or entirely sequence-independent (perhaps preferring only a particular purine or pyrimidine-purine pair), and might be executed by one of the pol III or TFIIIB subunits known to be located in the vicinity." Geiduschek EP & Kassavetis GA. (2001)

Initial phase of RNA chain elongation for RNAPIII Geiduschek EP & Kassavetis GA. (2001)

  • TFIIIB-pol III contact is not severed until several nucleotides have been incorporated
  • pol III abortively makes short txpts, mosty di- and tri-nucleotides and including hydrolytic cleavage products

Elongation Geiduschek EP & Kassavetis GA. (2001)

  • "RNA chain elongation (measured at each of 58 successive steps) proceeds unevenly, and particularly slowly where three UMP residues in succession are added."
  • "Pausing sets cycles of hydrolytic RNA chain retraction and resynthesis in motion."
  • "Pol III is termination-prone, consistent with its role in producing short transcripts. Short runs of U provoke termination" "Termination by

scpol III is accompanied by (extensive) generation of short oligonucleotides by hydrolytic cleavage at the RNA 30 end," "One can, therefore, regard the C11 subunit as the intrinsic termination factor of pol III."

Recycling (by RNAP III)

  • reinitiation of the same RNAP III complex at the same promoter that it just transcribed
  • thought to be particularly relevant to Pol III since it only transcribes short txn units, which are at times highly expressed

[edit] potential references for definitions

  • Specificity of TBP controlled by "proteins termed "activating factors," "coactivators," and/or "initiators" (2-6)" Librizzi et al. (1998)
  • Featherstone M. Coactivators in transcription initiation: here are your orders. Curr Opin Genet Dev. 2002 Apr;12(2):149-55. PMID:11893487
  • Naar AM, Lemon BD, Tjian R. Transcriptional coactivator complexes. Annu Rev Biochem. 2001;70:475-501. PMID:11395415

[edit] RNA polymerase III

transcription initiation factors - (Geiduschek EP & Kassavetis GA. 2001):

  1. TFIIIA
    • 5 S rRNA gene-specific DNA-binding factor
    • forms the platform for binding TFIIIC to these genes
  2. TFIIIC
    • recruits TFIIIB to its DNA sites upstream of the transcriptional start
    • binds DNA directly at the internal boxB and boxA promoter sites of tRNA (and similar) genes
    • hTFIIIC seems to have additional functions not shared by yTFIIIC,
      • hTFIIIC2 contains 3 HATs
      • hTFIIIC1 appears to have a direct role in polymerase recruitment independently of TFIIIC2
      • hTFIIIC0 "facilitates termination of transcription and contributes a factor that binds in the vicinity of the terminator"
    • TFIIIC "plays an important role in reserving pol III-transcribed genes for transcription in the face of competition by chromatin"
  3. TFIIIB
    • recruits pol III to the promoter
    • DNA binding factor brought to DNA in two ways:
      • binds directly to strong TATAs via TBP
      • through interaction with DNA-anchored TFIIIC
    • bends DNA (sharply)
    • involved in promoter opening (from deletions in both Brf and B)
  4. factors for vertebrate U class snRNAs
    1. Distal Sequence Element binding factors
      • DSE is compound element
      • bound by Oct-1 and Staf
    2. Proximal Sequence Element binding factors
      • bound by SNAPc (snRNA Activator Protein complex)
      • SNAPc is also a factor for pol II

negative regulators of RNAPIII:

  1. mammalian - three pleiotropic negative regulators: Dr1, p53 and RB (Geiduschek EP & Kassavetis GA. 2001)
    • Unphosphorylated RB suppresses pol III transcription by interactions with TFIIIB and TFIIIC2
    • Dr1, an abundant small nuclear phosphorylated protein, is a competing TBP ligand that sequesters TBP from its association with Brf (as well as TFIIB and TFIIA).179
    • interaction of p53 with Brf and TBP represses pol III transcription in vitro
  2. cerevisiae - MAF1
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