The April 2020 Editor's Choice article is “Long INterspersed Element‐1 Mobility as a Sensor of Environmental Stresses” (https://onlinelibrary.wiley.com/doi/10.1002/em.22366) by Brunella Del Re and Gianfranco Giorgi.
The putative junk DNA—long cast aside as non-essential—is now increasingly recognized for its essential role in gene expression regulation and disease onset. Of the various types of these junk DNA sequences, transposable elements (TEs), and more specifically, Long INterspersed elements (LINE-1, L1) account for 17% of the human genome. By engaging in the classical copy-paste mechanism, which involves reverse transcription of an RNA intermediate followed by insertion of the resulting cDNA copy at a new site (L1 retrotransposition (L1-RTP), LINE-1 increases genomic mutagenesis. Moreover, the onset of both neurological and oncological diseases in humans is associated with L1-RTP events. Typically, host cells employ epigenetic mechanisms to suppress LINE-1–dependent mutagenic events, but recent observations suggest that the relationship between LINE-1 and gene regulation is more dynamic than previously known.
In their most comprehensive and updated review, Del Re and Giorgi review details of not only the L1 retrotransposition events, their suppression mechanisms, and the two-step methodological strategy to study L1 regulation, but they also delineate how LINE-1 functions as a sensor of environmental stresses. Of significance is their detailed listing of the various environmental chemical agents (heavy metals, aluminum, arsenic, cadmium, cobalt, lead, mercury, nickel); carcinogens (benzo(a)pyrene, DMBA (7,12-Dimethylbenz[a]anthracene), TPA (12-Otetradecanoylphorbol-13-acetate), heterocyclic amines); drugs (antineoplastic, anti-inflammatory, lipid-lowering, psychoactive); other chemicals (oxidants, 6-Formylindolo[3,2-b ] carbazole, Capsaicin); environmental-physical agents (ionizing radiation, ultraviolet radiation, low-frequency magnetic fields, heat shock); experiential factors (running, post-weaning social isolation, maternal care, light/dark cycles). Within each category, they succinctly describe how each of these environmental perturbations alters expression and copy number changes in L1 activity, along with human health implications. Such a compendium enables an understanding of the current role of LINE-1 in sensing and commuting signals from the environment to physiologically relevant readouts. Furthermore, this systematic analysis allows for therapeutic potential in several human health conditions.