Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Alternative splicing (AS) enhances proteomic diversity in eukaryotes by selectively including or excluding exons.
• AS regulation involves spliceosomal components, RNA structures (e.g., G-quadruplexes), and liquid-liquid phase separation (LLPS) of splicing factors.
• Dysregulated AS is implicated in various human diseases, including cancers and neurodegenerative disorders.

Purpose of the Study:

• To systematically integrate current knowledge on alternative splicing regulation.
• To connect mechanistic insights of AS with emerging therapeutic strategies.
• To provide a framework for advancing RNA-targeted precision medicine.

Main Methods:

• Review of current literature on spliceosome architecture and dynamics.
• Analysis of structural RNA elements and LLPS-driven condensates in AS regulation.
• Appraisal of therapeutic innovations targeting aberrant splicing.

Main Results:

• AS is controlled by spliceosome, RNA structures, and LLPS-driven condensates.
• AS influences cell development, immunity, and stress adaptation.
• Aberrant splicing contributes to SF3B1 mutant cancers, TDP-43 neurodegeneration, and cardiovascular disease.

Conclusions:

• A unified framework integrating AS mechanisms and therapeutics is needed.
• Therapeutic strategies include small molecule modulators, antisense oligonucleotides, and CRISPR-based RNA editing.
• This integrated knowledge accelerates RNA-targeted precision medicine in the era of spatial multiomics and AI.