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| Status |
Public on Apr 21, 2023 |
| Title |
Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance [humanMut3primeseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We find disrupted nuclear RNA surveillance is oncogenic. Cyclin Dependent Kinase 13 (CDK13) is mutated in melanoma and patient-mutated CDK13 accelerates zebrafish melanoma. CDK13 mutation causes aberrant RNA stabilization. CDK13 is required for ZC3H14 phosphorylation, which is necessary and sufficient to promote nuclear RNA degradation. Mutant CDK13 fails to activate nuclear RNA surveillance, causing aberrant protein-coding transcripts to be stabilized and translated. Forced aberrant RNA expression accelerates melanoma in zebrafish. We find recurrent mutations in genes encoding nuclear RNA surveillance components in many malignancies, establishing nuclear RNA surveillance as a tumor-suppressive pathway. Activating nuclear RNA surveillance is crucial to avoid accumulation of aberrant RNAs and their ensuing consequences in development and disease.
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| Overall design |
3' RNA-seq data from the A375 melanoma cell line with perturbations of genes encoding PAXT modulators
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| Contributor(s) |
Insco ML, Abraham BJ, Dubbury SJ, Kaltheuner IH, Dust S, Wu C, Chen KY, Liu D, Bellaousov S, Cox AM, Martin BJ, Zhang T, Ludwig CG, Fabo T, Modhurima R, Esgdaille DE, Henriques T, Brown KM, Chanock SJ, Geyer M, Adelman K, Sharp PA, Young RA, Boutz PA, Zon LI |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jan 27, 2023 |
| Last update date |
Apr 23, 2023 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
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| Phone |
617-258-5219
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Young Lab
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| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (13)
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| GSM6998362 |
pLENTI_CMV_blast_CLOVER_into_A375s_Rep1 |
| GSM6998363 |
pLENTI_CMV_blast_CLOVER_into_A375s_Rep2 |
| GSM6998364 |
pLENTI_CMV_blast_CDK13_R860Q_into_A375s_Rep1 |
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| This SubSeries is part of SuperSeries: |
| GSE131334 |
Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance |
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| Relations |
| BioProject |
PRJNA928735 |
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