Martin J. Hicks, Chin-Rang Yang, and Klemens J. Hertel

RNA processing is carried out in close proximity to the site of transcription, allowing for cotranscriptional regulation of alternative pre-mRNA splicing. Here, we demonstrate that the coupling of RNA Pol II transcription and pre-mRNA splicing is required for efficient gene expression. Nascent pre-mRNAs are protected from nuclear degradation because the local concentration of the splicing machinery is sufficiently high to ensure its association over interactions with nucleases. Thus, the coupling of transcription and pre-mRNA splicing guarantees an efficient transfer from the transcription complex to the splicing machinery.

Because other RNA polymerases do not provide similar protection from nucleases, the physical link between transcription and RNA processing is RNA Pol II specific. We propose that the physical association of RNA processing and transcription is essential for maintaining efficient gene expression by ensuring an extended half-life of nascent pre-mRNAs. The mathematical model of transcription/RNA splicing coupling was built using kMech/Cellerator. The model was translated by Cellerator into 13 ODEs with 15 rate constants that describe the rates of change of 13 reactants involved in the model. Both RNA polymerase II and T7 RNA polymerase were simulated.

Documents for Download:
MathematicaTM executable, kMech.m, file : kMech
Instructions for kMech installation : Installation for kMech

The Mathematical Model of Transcription/RNA Splicing Coupling:
MathematicaTM notebook for RNA Polymerase II: Splicing_PolII

MathematicaTM notebook for T7 RNA Polymerase: Splicing_T7