Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron Splicing: Insights from Cryo-Electron Microscopy Structures
Autor: | Andrew J. Newman, Wojciech P. Galej, Kiyoshi Nagai, Navtej Toor |
---|---|
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Spliceosome RNA Splicing Group II intron splicing Crystallography X-Ray 03 medical and health sciences RNA Precursors RNA Messenger Phylogeny Cell Nucleus biology Chemistry Hydrolysis Cryoelectron Microscopy Intron RNA Active site Exons General Chemistry Group II intron Introns Cell biology 030104 developmental biology RNA splicing Spliceosomes biology.protein Nucleic Acid Conformation Precursor mRNA |
Zdroj: | Chemical Reviews. 118:4156-4176 |
ISSN: | 1520-6890 0009-2665 |
DOI: | 10.1021/acs.chemrev.7b00499 |
Popis: | Nuclear pre-mRNA splicing and group II intron self-splicing both proceed by two-step transesterification reactions via a lariat intron intermediate. Recently determined cryo-electron microscopy (cryo-EM) structures of catalytically active spliceosomes revealed the RNA-based catalytic core and showed how pre-mRNA substrates and reaction products are positioned in the active site. These findings highlight a strong structural similarity to the group II intron active site, strengthening the notion that group II introns and spliceosomes evolved from a common ancestor. Prp8, the largest and most conserved protein in the spliceosome, cradles the active site RNA. Prp8 and group II intron maturase have a similar domain architecture, suggesting that they also share a common evolutionary origin. The interactions between maturase and key group II intron RNA elements, such as the exon-binding loop and domains V and VI, are recapitulated in the interactions between Prp8 and key elements in the spliceosome's catalytic RNA core. Structural comparisons suggest that the extensive RNA scaffold of the group II intron was gradually replaced by proteins as the spliceosome evolved. A plausible model of spliceosome evolution is discussed. |
Databáze: | OpenAIRE |
Externí odkaz: |