Crystal structure of the 14-subunit RNA polymerase I

16 p.-5 fig.-8 extend. dat. fig.-1 extend. dat. tab.
Protein biosynthesis depends on the availability of ribosomes, which in turn relies on ribosomal RNA production. In eukaryotes, this process is carried out by RNA polymerase I (Pol I), a 14-subunit enzyme, the activity of which is a major determinant of cell growth. Here we present the crystal structure of Pol I from Saccharomyces cerevisiae at 3.0 Å resolution. The Pol I structure shows a compact core with a wide DNA-binding cleft and a tightly anchored stalk. An extended loop mimics the DNA backbone in the cleft and may be involved in regulating Pol I transcription. Subunit A12.2 extends from the A190 jaw to the active site and inserts a transcription elongation factor TFIIS-like zinc ribbon into the nucleotide triphosphate entry pore, providing insight into the role of A12.2 in RNA cleavage and Pol I insensitivity to α-amanitin. The A49–A34.5 heterodimer embraces subunit A135 through extended arms, thereby contacting and potentially regulating subunit A12.2.
M.M.-M. and U.J.R. were supported by EMBO Long-Term fellowships, M.M.-M. by the Marie-Curie fellowship (FP7-PEOPLE-2011-IEF 301002), N.M.I.T. by a Fundación Futuro fellowship, F.M.R. by an ESF/CSIC funded JAE-DOC contract and T.G. by the Volkswagen Stiftung via the Niedersachsenprofessur of Prof. G. M. Sheldrick. This work was also partly funded by grant BFU2010-16336 of the Spanish Ministry of Science.