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Background  The largest sub-unit of RNA polymerase II, Rpb1p, has long been known to be subject to post-translational modifications that influence various aspects of pre-mRNA processing. However, the portion of the Rpb1p molecule subject to these modifications – the carboxy-terminal domain or CTD – remains the subject of much fascination. Intriguingly, the CTD possesses a unique repetitive structure consisting of multiple repeats of the heptapeptide sequence, Y 1 S 2 P 3 T 4 S 5 P 6 S 7 . While these repeats are critical for viability, they are not required for basal transcriptional activity in vitro. This suggests that – even though the CTD is not catalytically essential – it must perform other critical functions in eukaryotes.    Presentation of the Hypothesis  By formally applying the long-standing mathematical principles of information theory, I explore the hypothesis that complex post-translational modifications of the CTD represent a means for the dynamic “programming” of Rpb1p and thus for the discrete modulation of the expression of specific gene subsets in eukaryotes.    Testing the Hypothesis  Empirical means for testing the informational capacity and regulatory potential of the CTD – based on simple genetic analysis in yeast model systems – are put forward and discussed.    Implications of the Hypothesis  These ideas imply that the controlled manipulation of CTD effectors could be used to “program” the CTD and thus to manipulate biological processes in eukaryotes in a definable manner.

Decoding the informational properties of the RNA polymerase II Carboxy Terminal Domain