Solution structure of the hRPABC14.4 subunit of human RNA polymerases

The protein hRPABC14.4 is an essential subunit of human RNA polymerases I, II, and III and is required for the transcription of all human nuclear gene s. The structure of hRPABC14.4 was determined by nuclear magnetic resonance spectroscopy. The protein fold comprises a highly conserved central domain forming two antiparallel alpha-helices flanked by the less conserved N- an d C-terminal regions forming a five-stranded beta-sandwich. Amino acids fro m the two helices participate in the generation of a hydrophobic surface ar ea which is conserved in all eukaryotic and archaeal homologous subunits, a nd likely constitutes a critical macromolecular interaction interface. The hRPABC14.4 structure accounts for mutagenesis results in Saccharomyces cere visiae and provides a structural working model for elucidating the role of this subunit in the molecular architecture and function of the human nuclea r RNA polymerases.