Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends

Abstract

The 3 ′ untranslated regions (3 ′ UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exon-isation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during hu-man genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3 ′ UTRs, thereby opening opportunities for differential post-transcriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3 ′ UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and eluci-date how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3 ′ UTRs