PEG10: Domesticated from Viruses, Unleashed in Disease

The influence of some retroelement-derived genes is conflicting: their adaptive role is essential to promote specific biological processes, while their dysregulation can have profound consequences in disease pathology. A prominent example of this is Paternally Expressed Gene 10 (PEG10), a member of the Mart family of retrotransposons that has both gag- and pol-like domains. PEG10 preserves many features that are shared with retrotransposons, including the ability to bind and package RNA into virus-like particles and to undergo self-processing through its aspartic protease domain. Here, we explore the role of PEG10 in both adaptive and pathological biology. Throughout evolution, PEG10 has been co-opted to support placental development, playing a vital role in fetal vasculature formation within the mouse placenta and in trophoblast cell differentiation. However, the accumulation of PEG10 has been identified in two neurological diseases, Angelman’s syndrome and Amyotrophic Lateral Sclerosis, and in numerous malignancies, where its activity may influence disease pathology. Although considerable progress has been made, the adaptive and putative pathological mechanisms of PEG10 activity remain elusive, and future work will aim to isolate the exact processes that govern PEG10’s ability to influence both placental development and disease pathology.