Branch-point Attack in Group II Introns is a Highly Reversible Transesterification, Providing a Potential Proofreading Mechanism for 5'-splice Site Selection

Overview

Journal RNA

Specialty Molecular Biology

Date 1995 Jun 1

PMID 7493317

Citations 33

Authors

K Chin

A M Pyle

Affiliations

Soon will be listed here.

Abstract

By examining the first step of group II intron splicing in the absence of the second step, we have found that there is an interplay of three distinct reactions at the 5'-splice site: branching, reverse branching, and hydrolytic cleavage. This approach has yielded the first kinetic parameters describing eukaryotic branching and establishes that group II intron catalysis can proceed on a rapid timescale. The efficient reversibility of the first step is due to increased conformational organization in the branched intermediate and it has several important mechanistic implications. Reversibility in the first step requires that the second step of splicing serve as a kinetic trap, thus driving splicing to completion and coordinating the first and second step of splicing. Facile reverse branching also provides the intron with a proofreading mechanism to control the fidelity of 5'-splice site selection and it provides a kinetic basis for the apparent mobility of group II introns.

Citing Articles

A new RNA-DNA interaction required for integration of group II intron retrotransposons into DNA targets.

Monachello D, Lauraine M, Gillot S, Michel F, Costa M Nucleic Acids Res. 2021; 49(21):12394-12410.

PMID: 34791436 PMC: 8643678. DOI: 10.1093/nar/gkab1031.

Cryo-EM Structures of a Group II Intron Reverse Splicing into DNA.

Haack D, Yan X, Zhang C, Hingey J, Lyumkis D, Baker T Cell. 2019; 178(3):612-623.e12.

PMID: 31348888 PMC: 6662634. DOI: 10.1016/j.cell.2019.06.035.

DNA cleavage and reverse splicing of ribonucleoprotein particles reconstituted with linear RmInt1 RNA.

Molina-Sanchez M, Toro N RNA Biol. 2019; 16(7):930-939.

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Small molecules that target group II introns are potent antifungal agents.

Fedorova O, Jagdmann Jr G, Adams R, Yuan L, Van Zandt M, Pyle A Nat Chem Biol. 2018; 14(12):1073-1078.

PMID: 30323219 PMC: 6239893. DOI: 10.1038/s41589-018-0142-0.

Activating the branch-forming splicing pathway by reengineering the ribozyme component of a natural group II intron.

Monachello D, Michel F, Costa M RNA. 2016; 22(3):443-55.

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