Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities

Area of Science:

• Molecular Biology
• Cancer Biology
• Biochemistry

Background:

• Alternative splicing and polyadenylation are crucial for gene expression and transcriptome diversity.
• Dysregulation of these RNA processing events is linked to cancer development, progression, and therapy resistance.
• Cancer cells' high transcriptional rates create vulnerabilities in pre-mRNA processing machinery.

Purpose of the Study:

• To review key findings on splicing factor kinases in cancer.
• To discuss the role of SRPK, CLK, and CDK in pre-mRNA processing.
• To explore therapeutic strategies targeting these kinases.

Main Methods:

• Literature review of studies on splicing factor kinases (SRPK, CLK, CDK).
• Analysis of kinase roles in alternative splicing and polyadenylation.
• Examination of kinase activity alterations in cancer cells.
• Review of preclinical and clinical data on kinase inhibitors in cancer therapy.

Main Results:

• SRPK, CLK, and CDK families play critical roles in regulating pre-mRNA processing.
• Altered kinase activity is observed in various human cancers.
• Inhibition of these kinases has demonstrated anticancer effects.
• Targeting splicing factor kinases exploits cancer cells' transcriptional addiction.

Conclusions:

• Splicing factor kinases are key regulators of RNA processing and are implicated in cancer.
• Inhibiting SRPK, CLK, and CDK presents a viable therapeutic avenue for cancer treatment.
• Further research into targeting these kinases holds promise for overcoming cancer therapy resistance.