Evidence for Co-Evolution between Human MicroRNAs and Alu-Repeats

Abstract

This paper connects Alu repeats, the most abundant repetitive elements in the human genome and microRNAs, small RNAs that alter gene expression at the post-transcriptional level. Base-pair complementarity could be demonstrated between the seed sequence of a subset of human microRNAs and Alu repeats that are integrated parallel (sense) in mRNAs. The most common target site coincides with the evolutionary most conserved part of Alu. A primate-specific gene cluster on chromosome 19 encodes the majority of miRNAs that target the most conserved sense Alu site. The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes. Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome. Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window. One hypothesis for this dual relationship is that these miRNAs could protect against too high rates of duplicative transposition, which would destroy the genome.

Do repeated arrays of regulatory small‐RNA genes elicit genomic imprinting?

“…In this context, amplification of microRNA genes at the C19MC locus was entangled with that of primate-specific Alu elements [70,81]. A similar emergence of microRNAs through species-specific TEs is also evident in marsupials [82], suggesting that it may constitute a previously unanticipated mode of small-RNA gene innovation in some mammalian lineages.…”

The role of Alu elements in the cis-regulation of RNA processing

“…By comparing pre-miRNA sequences with known repeat elements, they showed that transcription across repeat elements present in opposite orientations could explain the origin of several miRNAs. Since then, several independent investigations have increased the identification of TEderived miRNA loci in various mammal-and primatespecific genomes [108][109][110][111][112][113]. In the most recent report, an extensive analysis showed that about 15 % of all known miRNA genomic loci have a TE-origin [114].…”

“…In total, 50 % of the entire genomic region consists of repeat elements, and 90 % of these correspond to Alus. Based on the high enrichment of Alus in this region, the miRNA expansion in this cluster was proposed to be generated by Alu-mediated recombination events [121], leading to segmental duplications of 400-700 nt long cassettes which include one miRNA surrounded by several Alu elements in the reverse orientation [110,120].…”

MiRNAs’ Function and Role in Evolution: Under the View of Genomic Enhancement Phenomena

“…Despite this, genetic dosage effects of smaller scale are present in such species. Importantly, Lehnert et al [ 51 ] showed that sense Alu repeat sequences are enriched for miRNA target sites. Even more noteworthy, Li et al [ 52 ] and D'Antonio and Ciccrelli [ 53 ] found that miRNA targets are signifi cantly enriched for paralogs genes.…”