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-Structure paper
タイトル | Structure of the human RNA polymerase I elongation complex. |
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ジャーナル・号・ページ | Cell Discov, Vol. 7, Issue 1, Page 97, Year 2021 |
掲載日 | 2021年10月20日 |
著者 | Dan Zhao / Weida Liu / Ke Chen / Zihan Wu / Huirong Yang / Yanhui Xu / |
PubMed 要旨 | 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 ...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. |
リンク | Cell Discov / PubMed:34671025 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.81 - 3.01 Å |
構造データ | EMDB-31876, PDB-7vba: EMDB-31877, PDB-7vbb: EMDB-31878, PDB-7vbc: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-2TM: |
由来 |
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キーワード | TRANSCRIPTION/DNA/RNA / RNA Polymerase I / transcription / pre / state / TRANSCRIPTION-DNA-RNA complex / post state / back track state |