PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma
Details
Publication Year 2023,Volume 18,Issue #11,Page e0292278
Journal Title
PLoS One
Publication Type
Research article
Abstract
Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy.
Publisher
PLOS
Keywords
Humans; *Alternative Splicing; Protein-Arginine N-Methyltransferases/metabolism; Cell Line, Tumor; *Melanoma/drug therapy/genetics/metabolism; RNA Splicing; Cyclin-Dependent Kinase 4/genetics/metabolism
Department(s)
Laboratory Research
PubMed ID
37917641
Open Access at Publisher's Site
https://doi.org/10.1371/journal.pone.0292278
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2023-12-11 11:25:08
Last Modified: 2023-12-11 11:28:19

© 2024 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙