Hatchet ribozyme structure and implications for cleavage mechanism Journal Article
| Authors: | Zheng, L.; Falschlunger, C.; Huang, K.; Mairhofer, E.; Yuan, S.; Wang, J.; Patel, D. J.; Micura, R.; Ren, A. |
| Article Title: | Hatchet ribozyme structure and implications for cleavage mechanism |
| Abstract: | Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5′ nucleoside. The resulting modeled precatalytic conformation incorporates a splayed-apart alignment at the scissile phosphate, thereby providing structure-based insights into the in-line cleavage mechanism. We identify a guanine lining the catalytic pocket positioned to contribute to cleavage chemistry. The functional relevance of structure-based insights into hatchet ribozyme catalysis is strongly supported by cleavage assays monitoring the impact of selected nucleobase and atom-specific mutations on ribozyme activity. © 2019 National Academy of Sciences. All rights reserved. |
| Keywords: | catalysis; cleavage; noncoding rna; ribozyme; hatchet |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 116 |
| Issue: | 22 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2019-05-28 |
| Start Page: | 10783 |
| End Page: | 10791 |
| Language: | English |
| DOI: | 10.1073/pnas.1902413116 |
| PUBMED: | 31088965 |
| PROVIDER: | scopus |
| PMCID: | PMC6561176 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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