The RNAPII-CTD at the nexus of general and gene-specific regulation of transcription

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DNA contains the information necessary for life and accurate reading of this material is essential to adapt to changing environments. This is accomplished though a processed called transcription, during which the cell selects the genetic information to be read. RNA Polymerase II (RNAPII) is the molecular machine responsible for most transcription in the cell. It contains an extended region called the C-terminal domain (CTD). The CTD is important for all RNAPII-dependent transcription, given that it function as a platform for recruiting auxiliary factors required for this process. This activity is dependent on timely deposition and removal of modifications on the CTD. For example, the CTD modification status at the beginning of transcription differs from that of the end, allowing RNAPII to recruit specific factors at different stages of the process. The CTD is modified through the coordinated action of a number of enzymes in the cell, including Fcp1 and Cdk8. Fcp1 generally functions in recycling RNAPII by removing all CTD modifications following the end of transcription. This RNAPII can then be targeted by Cdk8, which blocks it from starting additional rounds of transcription, by prematurely modifying its CTD. As such, Fcp1 and Cdk8 play important roles in regulating the availability of RNAPII for transcription. ******Previously it was shown that shortening the CTD results in incorrect reading of genomic information, impaired ability to adapt to changing environments, altered CTD modification patters, and altered recruitment of factors necessary during transcription. Interestingly, the work described above also showed that while some of these effects were observed across all transcriptional units, others were confined to a smaller subset, switching our view of the RNAP-CTD as exclusively performing general functions, to being able to integrate regulatory signals in a specific manner. Our recent investigation of Fcp1 yielded similar findings as it revealed specific functions during transcription as it relates to the adaptation to high temperature and salt conditions. Here, we propose to tease apart general vs. specific functions of the RNAPII-CTD and Fcp1, and to identify factors and pathways that communicate with them to ensure correct reading of genetic information. **