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Series GSE223889 Query DataSets for GSE223889
Status Public on Apr 21, 2023
Title Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance [zf3primeseq]
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
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.
Overall design 3' RNA-seq data from the A375 melanoma cell line with perturbations of genes encoding PAXT modulators
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
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Submission date Jan 27, 2023
Last update date Apr 23, 2023
Contact name Richard A Young
Phone 617-258-5219
Organization name Whitehead Institute for Biomedical Research
Lab Young Lab
Street address 9 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL14875 Illumina HiSeq 2000 (Danio rerio)
Samples (6)
GSM6998356 Zebrafish_melanoma_eGFP_3pSeq_rep1
GSM6998357 Zebrafish_melanoma_eGFP_3pSeq_rep2
GSM6998358 Zebrafish_melanoma_eGFP_3pSeq_rep3
This SubSeries is part of SuperSeries:
GSE131334 Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance
BioProject PRJNA928736

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE223889_RAW.tar 6.0 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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