Inverted Alu repeats in loop-out exon skipping across hominoid evolution

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• RNA splicing diversifies the human genome's functional landscape.
• Distal intronic sequences' role in RNA splicing is underexplored.
• Inverted Alu elements may form RNA stem-loops, promoting exon skipping.

Purpose of the Study:

• To systematically analyze inverted Alu pairs in the human genome.
• To assess their impact on exon skipping via predicted RNA stem-loop formation.
• To determine their relevance to hominoid evolution.

Main Methods:

• Genome-wide analysis of inverted Alu pairs.
• Prediction of RNA stem-loop formation.
• Comparative genomic analysis across nine primate species.
• Experimental validation of exon skipping.

Main Results:

• Inverted Alu pairs, especially AluY-AluSx1 and AluSz-AluSx, are enriched near skippable exons.
• Stable stem-loop structures are predicted for these inverted Alu pairs.
• Hominoid-specific Alu insertions form inverted pairs enriched in skippable exons of ubiquitination pathway genes.
• Experimental validation confirmed exon skipping mediated by hominoid-specific inverted Alu pairs.

Conclusions:

• Inverted Alu pairs contribute to genomic innovation at the transcriptomic level.
• This work highlights a novel mechanism of transposable element-mediated evolution in hominoids.