Structure of the human RNA polymerase I elongation complex

• Published in: Cell discovery Vol. 7; no. 1; p. 97
• Main Authors: Zhao, Dan, Liu, Weida, Chen, Ke, Wu, Zihan, Yang, Huirong, Xu, Yanhui
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 20-10-2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/337/572; 631/535/1258/1259; Biomedical and Life Sciences; Catalysis; Cell Biology; Cell Culture; Cell Cycle Analysis; Cell Physiology; Deoxyribonucleic acid; DNA; DNA structure; DNA-directed RNA polymerase; Life Sciences; Proofreading; Ribosomal DNA; RNA polymerase; rRNA; Stem Cells; Transcription; Yeast
• ISSN: 2056-5968; 2056-5968
• DOI: 10.1038/s41421-021-00335-5

Eukaryotic RNA polymerase I (Pol I) transcribes ribosomal DNA and generates RNA for ribosome synthesis. Pol I accounts for the majority of cellular transcription activity and dysregulation of Pol I transcription leads to cancers and ribosomopathies. Despite extensive structural studies of yeast Pol I, structure of human Pol I remains unsolved. Here we determined the structures of the human Pol I in the pre-translocation, post-translocation, and backtracked states at near-atomic resolution. The single-subunit peripheral stalk lacks contacts with the DNA-binding clamp and is more flexible than the two-subunit stalk in yeast Pol I. Compared to yeast Pol I, human Pol I possesses a more closed clamp, which makes more contacts with DNA. The Pol I structure in the post-cleavage backtracked state shows that the C-terminal zinc ribbon of RPA12 inserts into an open funnel and facilitates “dinucleotide cleavage” on mismatched DNA–RNA hybrid. Critical disease-associated mutations are mapped on Pol I regions that are involved in catalysis and complex organization. In summary, the structures provide new sights into human Pol I complex organization and efficient proofreading.