The aim of the project was to analyse the functional role of Tyrosine-1 of mammalian RNA polymerase II CTD in the regulation of transcription-coupled processes. We studied mammalian CTD mutants to analyze the function of tyrosine1 residues. Mutation of 3/4 of the tyrosine residues in a mutant YFFF resulted in a massive read-through transcription phenotype. Read-through was observed for 3’ processed and polyadenylated RNAs. The YFFF mutant shows a loss of interaction with the Mediator and Integrator complexes in MS analysis.