The Evolutionarily Conserved Pol II Flap Loop Contributes to Proper Transcription Termination on Short Yeast Genes

Current models of transcription termination factor recruitment to the RNA polymerase II (Pol II) transcription complex rely exclusively on the direct interaction between the termination factor and phosphorylated isoforms of the Pol II C-terminal domain (CTD). Here, we report that the Pol II flap loop is needed for physical interaction of Pol II with the Pcf11/Clp1 sub-complex of cleavage factor IA (CF IA), which functions in both 3' end processing and Pol II termination, and for proper termination of short RNAs in vitro and in vivo. Deletion of the flap loop reduces the in vivo interaction of Pol II with CF IA but increases the association of Nrd1 during stages of the transcription cycle when the CTD is predominantly Ser5 phosphorylated. We propose a model in which the flap loop coordinates a binding equilibrium between the competing termination factors Pcf11 and Nrd1 to Pol II during termination of short RNA synthesis.