Crystal structure of the 14-subunit RNA polymerase I

• Published in: Nature (London) 2013-10, Vol.502 (7473), p.644-649
• Main Authors: Fernández-Tornero, Carlos, Moreno-Morcillo, María, Rashid, Umar J., Taylor, Nicholas M. I., Ruiz, Federico M., Gruene, Tim, Legrand, Pierre, Steuerwald, Ulrich, Müller, Christoph W.
• Format: Article
• Language: English
• Subjects: 631/337/1645; 631/337/572; 631/535/1266; Biosynthesis; Catalytic Domain; Crystal structure; Crystallography, X-Ray; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - metabolism; Enzymes; Humanities and Social Sciences; Models, Molecular; Molecular structure; multidisciplinary; Peptide Chain Elongation, Translational; Physiological aspects; Protein Binding; Protein biosynthesis; Protein Conformation; Protein Multimerization; Protein Subunits - chemistry; Ribosomes; RNA Polymerase I - chemistry; RNA Polymerase II - chemistry; RNA Polymerase III - chemistry; RNA polymerases; Saccharomyces cerevisiae - enzymology; Science; Transcription, Genetic; Transfer RNA
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12636

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. RNA polymerase (Pol) I transcribes ribosomal RNA that is critically required for ribosome assembly, and the enzyme is a major determinant of protein biosynthesis and cell growth; here the crystal structure of the complete 14-subunit Pol I from yeast is determined, providing insights into its unique architecture and the possible functional roles of its components. Pol I structure determined RNA polymerase I (Pol I) transcribes ribosomal RNA which is critically required for ribosome assembly, and the enzyme is therefore a major determinant of protein biosynthesis and cell growth. Mis-regulation of Pol I has been associated with several types of cancer, and Pol I is an emerging target for anticancer drugs. In this issue of Nature , two groups, working independently, present the X-ray crystal structure of the complete 14-subunit Pol I from yeast, determined at 3.0 Å and 2.8 Å resolution. The basic architecture of Pol I resembles those of Pol II and Pol III, but its DNA-binding cleft adopts a wider conformation than seen in the other RNA polymerases, and other unique features also provide insights into the functional roles of its components.