Alu-mediated RNA duplexes are associated with widespread exon skipping across primate transcriptomes

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Alternative splicing patterns exhibit rapid divergence across vertebrate evolution.
• Understanding the mechanisms driving these evolutionary changes is crucial for deciphering gene regulation complexity.

Purpose of the Study:

• To investigate the role of RNA duplexes, particularly those involving Alu elements, in shaping alternative splicing evolution.
• To identify RNA binding proteins that regulate Alu-mediated alternative splicing.

Main Methods:

• Genome-wide prediction of stable RNA duplexes.
• Analysis of alternative splicing profiles.
• Proximity ligation-detection of RNA-RNA interactions.
• Identification of RNA binding protein interactions.

Main Results:

• The majority of long-range intronic RNA duplexes are mediated by inverted Alu-repeat elements.
• These Alu-derived RNA duplexes are associated with divergent exon skipping patterns in primates.
• RNA binding proteins HNRNPC, ILF2, and ILF3 directly control Alu duplex-associated alternative splicing levels.

Conclusions:

• Alu-derived RNA duplexes play a significant role in the divergence of alternative splicing patterns during mammalian evolution.
• Modulation of these duplexes by specific RNA binding proteins contributes to species-specific gene regulation.