mRNA structure determines modification by pseudouridine synthase 1
| Autor: | Thomas M. Carlile, Wendy V. Gilbert, Tristan A Bell, Nicole M. Martinez, Boris Zinshteyn, Amanda Su, Cassandra Schaening |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Saccharomyces cerevisiae
medicine.disease_cause Article Gene Expression Regulation Enzymologic Pseudouridine 03 medical and health sciences chemistry.chemical_compound Gene Expression Regulation Fungal Gene expression medicine Humans RNA Messenger Nucleic acid structure Structural motif Molecular Biology Hydro-Lyases 030304 developmental biology Regulation of gene expression 0303 health sciences Messenger RNA Mutation Chemistry 030302 biochemistry & molecular biology RNA Cell Biology Cell biology Nucleic Acid Conformation |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | Pseudouridine (Ψ) is a post-transcriptional RNA modification that alters RNA-RNA and RNA-protein interactions that affect gene expression. mRNA pseudouridylation was recently discovered as a widespread and conserved phenomenon, but the mechanisms responsible for selective, regulated pseudouridylation of specific sequences within mRNAs were unknown. Here, we have revealed new mRNA targets for five pseudouridine synthases and probed the determinants of mRNA target recognition by the predominant mRNA pseudouridylating enzyme, Pus1, by developing high-throughput kinetic analysis of pseudouridylation in vitro. Combining computational prediction and rational mutational analysis revealed an RNA structural motif that is both necessary and sufficient for mRNA pseudouridylation. Applying this structural context information predicted hundreds of additional mRNA targets, that we showed were pseudouridylated in vivo. These results demonstrate a structure-dependent mode of mRNA target recognition by a conserved pseudouridine synthase and implicate modulation of RNA structure as the likely mechanism to regulate mRNA pseudouridylation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink