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

Abstract

Doc number: 241

Abstract

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 S₂ P₃ T₄ S₅ P₆ S₇ . 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.