BioProject

RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. More...

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: V6.5 mouse embryonic stem cells with endogenous Cdk13 knock out complemented by doxycycline (Dox)-inducible Flag- HA- epitope tagged Cdk13 transgene (Cdk13△) were grown in the presence of Cdk13 (+Dox) or were depleted of Cdk13 (-Dox). RNA sequencing experimental design: PolyA-selected RNA was isolated from two independently derived Cdk13△ clones each in biological duplicate for cells maintained in Dox (+Dox), withdrawn from Dox for 48 hours (-Dox 48hrs), or withdrawn from Dox for 72 hours (-Dox 72hrs). A total of 12 libraries were prepared and sequenced. Less...