PT - JOURNAL ARTICLE AU - Melvin Noe Gonzalez AU - Shigeo Sato AU - Chieri Tomomori-Sato AU - Joan W. Conaway AU - Ronald C. Conaway TI - CTD-dependent and - independent mechanisms govern co-transcriptional capping of Pol II transcripts AID - 10.1101/269977 DP - 2018 Jan 01 TA - bioRxiv PG - 269977 4099 - http://biorxiv.org/content/early/2018/02/25/269977.short 4100 - http://biorxiv.org/content/early/2018/02/25/269977.full AB - Co-transcriptional capping of RNA polymerase II (Pol II) transcripts by capping enzyme proceeds orders of magnitude more efficiently than capping of free RNA. Previous studies brought to light a role for the phosphorylated Pol II CTD in activation of co-transcriptional capping; however, CTD phosphorylation alone could not account for the observed magnitude of activation. Here, we exploit a defined Pol II transcription system that supports both CTD phosphorylation and robust activation of capping to dissect the mechanism of co-transcriptional capping. Taken together, our findings identify a novel CTD-independent, but Pol II-mediated, mechanism that functions in parallel with CTD-dependent processes to ensure optimal capping, and they support a “tethering” model for the mechanism of activation.