Rearrangements within the U6 snRNA Core during the Transition between the Two Catalytic Steps of Splicing
| Autor: | Katarzyna Matylla-Kulińska, Katarzyna Eysmont, Maria M. Konarska, Agata Jaskulska, Marcin Magnus |
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| Rok vydání: | 2019 |
| Předmět: |
Spliceosome
Saccharomyces cerevisiae Proteins Ribonucleoprotein U4-U6 Small Nuclear Saccharomyces cerevisiae Biology Catalysis 03 medical and health sciences 0302 clinical medicine RNA Small Nuclear Molecular Biology 030304 developmental biology Adenosine Triphosphatases 0303 health sciences Transition (genetics) Cryoelectron Microscopy RNA Cell Biology Group II intron Introns Alternative Splicing Intramolecular force Mutation RNA splicing Spliceosomes Biophysics Nucleic Acid Conformation RNA Splicing Factors RNA Helicases 030217 neurology & neurosurgery Small nuclear RNA |
| Zdroj: | Molecular Cell. 75:538-548.e3 |
| ISSN: | 1097-2765 |
| Popis: | The RNA catalytic core of spliceosomes as visualized by cryoelectron microscopy (cryo-EM) remains unchanged at different stages of splicing. However, we demonstrate that mutations within the core of yeast U6 snRNA modulate conformational changes between the two catalytic steps. We propose that the intramolecular stem-loop (ISL) of U6 exists in two competing states, changing between a default, non-catalytic conformation and a transient, catalytic conformation. Whereas stable interactions in the catalytic triplex promote catalysis and their disruptions favor exit from the catalytic conformation, destabilization of the lower ISL stem promotes catalysis and its stabilization supports exit from the catalytic conformation. Thus, in addition to the catalytic triplex, U6-ISL acts as an important dynamic component of the catalytic center. The relative flexibility of the lower U6-ISL stem is conserved across eukaryotes. Similar features are found in U6atac and domain V of group II introns, arguing for the generality of the proposed mechanism. |
| Databáze: | OpenAIRE |
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