Using Alu Elements As Polyadenylation Sites: A Case of Retroposon Exaptation

Of the 1.1 million Alu retroposons in the human genome, about 10,000 are inserted in the 3' untranslated regions (UTR) of protein-coding genes and 1% of these (107 events) are active as polyadenylation sites (PASs). Strikingly, although Alu's in 3' UTR are indifferently inserted in the forward or reverse direction, 99% of polyadenylation-active Alu sequences are forward oriented. Consensus Alu+ sequences contain sites that can give rise to polyadenylation signals and enhancers through a few point mutations. We found that the strand bias of polyadenylation-active Alu's reflects a radical difference in the fitness of sense and antisense Alu's toward cleavage/polyadenylation activity. In contrast to previous beliefs, Alu inserts do not necessarily represent weak or cryptic PASs; instead, they often constitute the major or the unique PAS in a gene, adding to the growing list of Alu exaptations. Finally, some Alu-borne PASs are intronic and produce truncated transcripts that may impact gene function and/or contribute to gene remodeling.