Detection of Alu Exonization Events in Human Frontal Cortex From RNA-Seq Data

Alu exonization events functionally diversify the transcriptome, creating alternative mRNA isoforms and accounting for an estimated 5% of the alternatively spliced (skipped) exons in the human genome. We developed computational methods, implemented into a software called Alubaster, for detecting incorporation of Alu sequences in mRNA transcripts from large scale RNA-seq data sets. The approach detects Alu sequences derived from both fixed and polymorphic Alu elements, including Alu insertions missing from the reference genome. We applied our methods to 117 GTEx human frontal cortex samples to build and characterize a collection of Alu-containing mRNAs. In particular, we detected and characterized Alu exonizations occurring at 870 fixed Alu loci, of which 237 were novel, as well as hundreds of putative events involving Alu elements that are polymorphic variants or rare alleles not present in the reference genome. These methods and annotations represent a unique and valuable resource that can be used to understand the characteristics of Alu-containing mRNAs and their tissue-specific expression patterns.

Automated summary

Alu exonization events contribute to 5% of alternatively spliced exons in the human genome, and computational methods have been developed to detect Alu sequences in mRNA transcripts. Analysis of 117 GTEx human frontal cortex samples revealed hundreds of Alu-containing mRNAs, including both fixed Alu loci and polymorphic Alu elements. This unique resource provides valuable insights into the characteristics and tissue-specific expression patterns of Alu-containing mRNAs.