MicroRNA retrocopies generated via L1-mediated retrotransposition in placental mammals help to reveal how their parental genes were transcribed.

In mammalian genomes, most retrocopies emerged via the L1 retrotransposition machinery. The hallmarks of an L1-mediated retrocopy, i.e., the intronlessness, the presence of a 3' poly-A tail, and the TSDs at both ends, were frequently used to identify retrotransposition events. However, most previous studies only focused on protein-coding genes as their possible parental sources and thus only a few retrocopies derived from non-coding genes were reported. Remarkably, none of them was from microRNAs. Here in this study, we found several retrocopies generated from the mir-302-367 cluster gene (MIR302CHG), and identified a novel alternatively spliced exon encoding mir-302a. The other recognized microRNA retrotransposition events are primate-specific with mir-373 and mir-498 as their parental genes. The 3' poly-A tracts of these two retrocopy groups were directly attached to the end of the microRNA precursor homologous regions, which suggests that their parental transcripts might alternatively terminate at the end of mir-373 and mir-498. All the three parental microRNAs are highly expressed in specific tissues with elevated retrotransposon activity, such as the embryonic stem cells and the placenta. This might be the reason that our first microRNA retrocopy findings were derived from these three microRNA genes.