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| Status |
Public on Jun 26, 2023 |
| Title |
Co-transcriptional pseudouridylation of mRNAs by the H/ACA complex controls translational efficiency [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Post-transcriptional modifications of mRNA have emerged as novel regulators of gene expression. Pseudouridylation is the most abundant and widespread type of RNA modification in living organisms; however, the biological role of pseudouridine in mRNAs remains poorly understood. Here, we show that the pseudouridine synthase dyskerin associates with RNA polymerase II and is enriched at RNA polymerase II-transcribed genes genome-wide. As part of the H/ACA complex, dyskerin binds to thousands of mRNAs and is responsible for their pseudouridylation, an action that occurs in chromatin and does not appear to require a fully complementary guide RNA. In cells lacking dyskerin, pseudouridylation of mRNAs is reduced, while at the same time, de novo protein production is enhanced, indicating that pseudouridylation of mRNAs by dyskerin interferes with translation. Accordingly, pseudouridylation of an mRNA by dyskerin in vitro results in reduced translation of that mRNA. Moreover, in patients with dyskeratosis congenita caused by inherited mutations in the DKC1 gene, binding between mutated dyskerin and mRNAs is altered and pseudouridylation of mRNAs severely reduced. Our findings reveal a new critical function of the H/ACA complex in directing translation control with important implications for development and disease.
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| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for RNAPII and dyskerin in U2OS and HCT116 cells.
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| Contributor(s) |
Pederiva C, Agostini F |
| Citation(s) |
37506213 |
| |
| Submission date |
Aug 14, 2022 |
| Last update date |
Sep 25, 2023 |
| Contact name |
Federico Agostini |
| E-mail(s) |
[email protected]
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| Organization name |
Science for Life Laboratories
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| Street address |
Tomtebodavägen 23a
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| City |
Solna |
| State/province |
Stockholm |
| ZIP/Postal code |
171 65 |
| Country |
Sweden |
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| Platforms (2) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE211202 |
Co-transcriptional pseudouridylation of mRNAs by the H/ACA complex controls translational efficiency. |
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| Relations |
| BioProject |
PRJNA869466 |
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