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Publication Abstract from PubMed

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-A 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.

Hatchet ribozyme structure and implications for cleavage mechanism.,Zheng L, Falschlunger C, Huang K, Mairhofer E, Yuan S, Wang J, Patel DJ, Micura R, Ren A Proc Natl Acad Sci U S A. 2019 May 28;116(22):10783-10791. doi:, 10.1073/pnas.1902413116. Epub 2019 May 14. PMID:31088965^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.