Functional heritage: the evolution of chimeric RNA into a gene

Once believed to be unique features of neoplasia, chimeric RNAs have been discovered in normal physiology. We speculated that some chimeric RNAs may be functional precursors of genes and that forming chimeric RNA at the transcriptional level may be a “trial” mechanism before the functional element is fixed into the genome. Supporting this idea, we identified a chimeric RNA, HNRNPA1L2-SUGT1 (H-S), whose sequence is highly similar to the pseudogene MRPS31P5. Evolutionarily, H-S precedes MRPS31P5, as it can be detected bioinformatically and experimentally in marmoset monkeys, which do not possess MRPS31P5 in their genome. Conversely, H-S is minimally expressed in humans, while instead, MRPS31P5 is abundantly expressed. Here, we provide multiple lines of evidence supporting that MRPS31P5 is not truly a pseudogene, but a functional descendent of the H-S chimera. We also show that H-S is a product of cis-splicing between adjacent genes, while MRPS31P5 is likely produced by genome rearrangement. Human foreskin fibroblast cell transfected with si-hMRPS31P5 and si-gl2, marmoset fibroblast cell CJ-157 cell transfected with si-HNRNPA1L2-SUGT1 and si-gl2 were subjected to RNA sequence