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Abstract
The 3′ untranslated regions (3′ UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human 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 posttranscriptional 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 elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3′ UTRs.
Highlights
The 3 untranslated regions (3 UTRs) of transcripts are important for gene expression regulation
We demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3 UTRs
They are located downstream of the last polyadenylation site, but are connected via splice junctions to positions within the gene boundaries (Figure 1A), suggesting that they are transcribed as part of the primary transcript
Summary
The 3 untranslated regions (3 UTRs) of transcripts are important for gene expression regulation. More than 50% of human genes give rise to multiple isoforms with alternative 3 UTRs, thereby enabling tissue-specific or developmental regulation of transcripts that otherwise encode for the same protein function [1]. A prevalent mechanism to generate alternative 3 UTRs is the usage of alternative terminal exons and polyadenylation signals (PASs) that trigger endonucleolytic cleavage and addition of the polyadenosine (polyA) tail. Despite their importance the evolution of alternative 3 UTRs has received little attention to date. Whereas considerable attention has been paid to the interference of intronic Alu elements with splicing, the effect of Alu elements in the intergenic regions in the neighbourhood of genes remained largely unexplored
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