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RNA polymerase II (Pol II) is an enzyme that is composed of twelve subunits and is responsible for the transcription of protein-coding genes. Transcription initiation requires Pol II-mediated recruitment of transcription machinery to a target promoter, thereby allowing transcription to begin. The largest subunit of Pol II (referred to as RPB1 or RPB205) is a 1,840 amino acid protein that contains one C2H2-type zinc finger and a C-terminal domain comprised of several heptapeptide repeats. Although Pol II function requires the cooperation of all twelve subunits, the largest subunit conveys Pol II catalytic activity and, together with the second largest subunit, forms the active center of the Pol II enzyme. Additionally, the large subunit participates in forming the DNA-binding domain of Pol II, a groove that is necessary for transcription of the DNA template. Without proper function of the large subunit, mRNA synthesis and subsequent transcription elongation cannot occur.