Cross-Talk of Phosphorylation and Prolyl Isomerization of the C-terminal Domain of RNA Polymerase II

Abstract

Post-translational modifications of the heptad repeat sequences in the C-terminal domain (CTD) of RNA polymerase II (Pol II) are well recognized for their roles in coordinating transcription with other nuclear processes that impinge upon transcription by the Pol II machinery; and this is primarily achieved through CTD interactions with the various nuclear factors. The identification of novel modifications on new regulatory sites of the CTD suggests that, instead of an independent action for all modifications on CTD, a combinatorial effect is in operation. In this review we focus on two well-characterized modifications of the CTD, namely serine phosphorylation and prolyl isomerization, and discuss the complex interplay between the enzymes modifying their respective regulatory sites. We summarize the current understanding of how the prolyl isomerization state of the CTD dictates the specificity of writers (CTD kinases), erasers (CTD phosphatases) and readers (CTD binding proteins) and how that correlates to transcription status. Subtle changes in prolyl isomerization states cannot be detected at the primary sequence level, we describe the methods that have been utilized to investigate this mode of regulation. Finally, a general model of how prolyl isomerization regulates the phosphorylation state of CTD, and therefore transcription-coupled processes, is proposed.

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“…3F ). However, different from the positively charged triad of Lys63, Arg68 and Arg69, these additional interactions have been suggested to facilitate the PIN1-catalyzed isomerization reaction 54 . In consistent, we found that mutation of T204 to alanine abolished the interaction between PIN1 and BRD4 in cultured cells ( Fig.…”

Intrinsic Disorder and Posttranslational Modifications: The Darker Side of the Biological Dark Matter

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