A rule-based kinetic model of RNA polymerase II C-terminal domain phosphorylation

Stuart Aitken, Ross D. Alexander*, Jean D. Beggs

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    4 Citations (Scopus)

    Abstract

    The complexity ofmany RNA processing pathways is such that a conventional systemsmodelling approach is inadequate to represent all themolecular species involved. We demonstrate that rule-based modelling permits a detailed model of a complex RNA signalling pathway to be defined. Phosphorylation of the RNApolymerase II (RNAPII)C-terminal domain (CTD; a flexible tail-like extension of the largest subunit) couples pre-messenger RNA capping, splicing and 30 end maturation to transcriptional elongation and termination, and plays a central role in integrating these processes. The phosphorylation states of the serine residues of many heptapeptide repeats of the CTD alter along the coding region of genes as a function of distance from the promoter. From a mechanistic perspective, both the changes in phosphorylation and the location atwhich they take place on the genes are a function of the time spent byRNAPII in elongation as this interval provides the opportunity for the kinases and phosphatases to interactwith theCTD.On this basis,we synthesize the available data to create a kinetic model of the action of the known kinases and phosphatases to resolve the phosphorylation pathways and their kinetics.

    Original languageEnglish
    Article number0438
    JournalJournal of the Royal Society Interface
    Volume10
    Issue number86
    DOIs
    Publication statusPublished - 6 Sep 2013

    Keywords

    • Kappa
    • Rule-based modelling
    • Transcription

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