Coupling of alternative splicing and alternative polyadenylation

Area of Science:

• Molecular Biology
• RNA Processing

Background:

• RNA splicing and 3'-cleavage and polyadenylation (CPA) are fundamental RNA maturation processes.
• Alternative splicing (AS) and alternative polyadenylation (APA) are key regulatory events.
• Emerging evidence highlights crosstalk between splicing and 3'-end processing.

Purpose of the Study:

• To review the molecular machinery of splicing and 3'-end processing.
• To examine the functions and mechanisms of crosstalk between these processes.
• To discuss the role of long-read sequencing in studying AS-APA coordination.

Main Methods:

• Literature review of recent studies on splicing and 3'-end processing crosstalk.
• Analysis of molecular mechanisms and functions involved.
• Discussion of technological advancements, including long-read sequencing.

Main Results:

• 3'-end processing factors and poly(A) tails can promote last intron splicing and influence exon splicing.
• 3'-end processing factors interact with RNA-binding proteins (RBPs) to regulate AS.
• Splicing affects 3'-end processing, with some RBPs having dual roles.
• Splicing within the 3' untranslated region (3' UTR) contributes to 3' UTR diversity.

Conclusions:

• Crosstalk between RNA splicing and 3'-end processing is integral to RNA regulation.
• Understanding this coordination is vital for disease diagnosis and treatment strategies.
• Long-read sequencing offers powerful insights into coupled AS-APA events.