The Interplay of Splicing and Metabolism in Cancer

Area of Science:

• Oncology
• Molecular Biology
• Metabolism

Background:

• Aberrant RNA splicing and metabolic reprogramming are key cancer hallmarks.
• These processes were historically viewed as separate but show extensive crosstalk.
• Recent evidence highlights reciprocal influences between RNA splicing and cellular metabolism.

Purpose of the Study:

• To synthesize mechanistic insights into splicing's regulation of metabolic adaptation in cancer.
• To review how oncogenic mutations and RNA-binding proteins (RBPs) drive alternative splicing in metabolic regulators.
• To examine the direct modulation of splicing by metabolites and nutrient-sensing pathways.

Main Methods:

• Literature review synthesizing recent mechanistic insights.
• Discussion of oncogenic mutations in spliceosomal components.
• Examination of RNA-binding protein dysregulation and metabolite-mediated splicing modulation.

Main Results:

• Splicing programs significantly regulate metabolic adaptation in various cancer types.
• Mutations in spliceosomal components and RBPs promote metabolic plasticity via alternative splicing.
• Metabolites and nutrient-sensing pathways directly impact splicing factor activity and spliceosome dynamics.
• A novel mitochondrial quality control mechanism involving retrograde signals to the spliceosome for mitophagy was identified.

Conclusions:

• The interplay between RNA splicing and metabolism is crucial for cancer progression.
• Targeting this crosstalk offers potential therapeutic strategies.
• Understanding these mechanisms enhances knowledge of cancer adaptation and mitochondrial homeostasis.