Prp8 positioning of U5 snRNA is linked to 5' splice site recognition
| Autor: | Melissa S. Jurica, Alma L. Burlingame, Andrew J. MacRae, Robert J. Chalkley, Megan Mayerle, Christine Guthrie, Eva Hrabeta-Robinson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Spliceosome Ribonucleoprotein U4-U6 Small Nuclear GTPase U4-U6 Small Nuclear Saccharomyces cerevisiae Prp8 03 medical and health sciences U5 Small Nuclear Small Nuclear Catalytic Domain RNA Small Nuclear Report Genetics RNA Precursors Humans 5′ exon Molecular Biology Ribonucleoprotein U5 Small Nuclear chemistry.chemical_classification ' exon biology Mutagenesis Intron Neurosciences Active site RNA-Binding Proteins Ribonucleoprotein Amino acid Cell biology U5 snRNA 030104 developmental biology chemistry RNA splicing pre-mRNA splicing biology.protein chemical probing Spliceosomes RNA Generic health relevance Biochemistry and Cell Biology RNA Splice Sites spliceosome Small nuclear RNA Developmental Biology |
| Zdroj: | RNA (New York, N.Y.), vol 24, iss 6 |
| ISSN: | 1469-9001 |
| Popis: | Prp8 is an essential protein that regulates spliceosome assembly and conformation during pre-mRNA splicing. Recent cryo-EM structures of the spliceosome model Prp8 as a scaffold for the spliceosome's catalytic U snRNA components. Using a new amino acid probing strategy, we identified a dynamic region in human Prp8 that is positioned to stabilize the pre-mRNA in the spliceosome active site through interactions with U5 snRNA. Mutagenesis of the identified Prp8 residues in yeast indicates a role in 5′ splice site recognition. Genetic interactions with spliceosome proteins Isy1, which buttresses the intron branch point, and Snu114, a regulatory GTPase that directly contacts Prp8, further corroborate a role for the same Prp8 residues in substrate positioning and activation. Together the data suggest that adjustments in interactions between Prp8 and U5 snRNA help establish proper positioning of the pre-mRNA into the active site to enhance 5′ splice site fidelity. |
| Databáze: | OpenAIRE |
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