Abstract
Since the discovery of the high abundance of Alu elements in the human genome, the interest for the functional significance of these retrotransposons has been increasing. Primate Alu and rodent Alu-like elements are retrotransposed by a mechanism driven by the LINE1 (L1) encoded proteins, the same machinery that generates the L1 repeats, the processed pseudogenes (PPs), and other retroelements. Apart from free Alu RNAs, Alus are also transcribed and retrotranscribed as part of cellular gene transcripts, generally embedded inside 3’ untranslated regions (UTRs). Despite different proposed hypotheses, the functional implication of the presence of Alus inside 3’UTRs remains elusive. In this study we hypothesized that Alu elements in 3’UTRs could be involved in the genesis of PPs. By analyzing human genome data we discovered that the existence of 3’UTR-embedded Alu elements is overrepresented in genes source of PPs. In contrast, the presence of other retrotransposable elements in 3’UTRs does not show this PP linked overrepresentation. This research was extended to mouse and rat genomes and the results accordingly reveal overrepresentation of 3’UTR-embedded B1 (Alu-like) elements in PP parent genes. Interestingly, we also demonstrated that the overrepresentation of 3’UTR-embedded Alus is particularly significant in PP parent genes with low germline gene expression level. Finally, we provide data that support the hypothesis that the L1 machinery is also the system that herpesviruses, and possibly other large DNA viruses, use to capture host genes expressed in germline or somatic cells. Altogether our results suggest a novel role for Alu or Alu-like elements inside 3’UTRs as facilitators of the genesis of PPs, particularly in lowly expressed genes. Moreover, we propose that this L1-driven mechanism, aided by the presence of 3’UTR-embedded Alus, may also be exploited by DNA viruses to incorporate host genes to their viral genomes.
Highlights
Alu elements are the most abundant repetitive elements in the human genome; with 1.1 million copies, they represent about 10% of the genome [1, 2]
These results suggest a novel role of Alus: 3’untranslated regions (UTRs)-embedded Alu or Alu-like elements facilitate the genesis of processed pseudogenes by L1 products
In contrast with the Alu elements, we found that the presence of other short interspersed nucleotide elements (SINEs) in the 3’UTR (s) is underrepresented in human processed pseudogenes (PPs) parent genes (Fig 1B; P < 0.02, χ2 test); 12.54% of genes with PPs have non-Alu SINEs in their 3’UTR, compared with 14.60% of genes without PPs
Summary
Alu elements are the most abundant repetitive elements in the human genome; with 1.1 million copies, they represent about 10% of the genome [1, 2] They have a length of approximately 300 bp and a dimeric structure, with two similar but distinct monomers joined by an A-rich linker and followed by a short poly(A) tail. These kinds of short interspersed nucleotide elements (SINEs) are retrotransposons specific to primates. The total number of copies of B1, B2, B4, and ID elements in mouse (1.4 millions) surpasses that of human Alu elements [7] Both primates and rodents have MIR (mammalian-wide interspersed repeat) elements, which are ancient tRNA-derived SINEs
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