Environmental Health and Long Non-coding RNAs

Abstract

An individual's risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation. This review aims to provide a general overview of lncRNA function with a focus on their role as key regulators of health and disease and as biomarkers of environmental exposure.

Keywords: Chemicals; Disease; Epigenetics; LncRNA; Smoking; Toxicology.

Figure 1

Example of lncRNA cellular functions. LncRNAs can bind to DNA, RNA, and proteins and act in diverse ways within the cell. LncRNAs regulate gene expression by multiple mechanisms. They can guide chromatin remodeling complexes to the correct chromosomal locations controlling the balance between transcriptionally active euchromatin and silent heterochromatin both locally and globally (A). Furthermore, lncRNAs can inhibit or facilitate the recruitment of RNA pol II, transcription factors and/or cofactors to gene promoters, thereby controlling transcription of target genes (B). They can regulate alternative splicing of pre-mRNAs and thereby contribute to the transcriptome complexity (C). Moreover, they can affect the stability and translation of mRNA by base-pairing with mRNA molecules (D). LncRNAs can compete for miRNA binding and thereby preventing their function and influencing the expression of miRNA target gene expression (E). They can also be processed into small, single- or double-stranded RNAs that act as siRNAs and target other RNAs, which subsequently could result in target degradation (F). Their flexible scaffold nature enables lncRNAs to join multiple protein factors that would not interact or functionally cooperate if they only relied on protein–protein interactions (G). The scaffold function is also important for protein activity and localization as well as subcellular structures (H, I). (Adapted from: Gutschner T, Diederichs S: The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012 Jun;9(6):703–19) [59].