Crystal structure of Pistol, a class of self-cleaving ribozyme

Nguyen, Laura A.; Wang, Jimin; Steitz, Thomas A.

doi:10.1073/pnas.1611191114

Title: Crystal structure of Pistol, a class of self-cleaving ribozyme

Journal Article · Tue Jan 17 00:00:00 EST 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1611191114· OSTI ID:1343147

Nguyen, Laura A. ^[1]; Wang, Jimin ^[1]; Steitz, Thomas A. ^[2]

Yale Univ., New Haven, CT (United States)
Yale Univ., New Haven, CT (United States). Howard Hughes Medical Inst. and Dept. of Chemistry

Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation. Comparative genomic analysis has led to the discovery of a new class of small self-cleaving ribozymes named Pistol. We report herein the crystal structure of Pistol at 2.97-Å resolution. Our results suggest that the Pistol ribozyme self-cleavage mechanism likely uses a guanine base in the active site pocket to carry out the phosphoester transfer reaction. The guanine G40 is in close proximity to serve as the general base for activating the nucleophile by deprotonating the 2'-hydroxyl to initiate the reaction (phosphoester transfer). Furthermore, G40 can also establish hydrogen bonding interactions with the nonbridging oxygen of the scissile phosphate. The proximity of G32 to the O5' leaving group suggests that G32 may putatively serve as the general acid. The RNA structure of Pistol also contains A-minor interactions, which seem to be important to maintain its tertiary structure and compact fold. Our findings expand the repertoire of ribozyme structures and highlight the conserved evolutionary mechanism used by ribozymes for catalysis.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE; Howard Hughes Medical Institute; National Institutes of Health (NIH)

Grant/Contract Number:: 5 F32AI114095-02

OSTI ID:: 1343147

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 5; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 33 works

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Title: Crystal structure of Pistol, a class of self-cleaving ribozyme

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