Abstract
Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study.
Highlights
Whole-genome sequencing studies reveal that our genome comprises approximately 3 to 3.2 billion base pairs of DNA, but merely 1–2% of those pairs correspond to the annotated exons of protein-coding genes
Perspectives circRNAs are increasingly being recognized to play essential roles in several diseases including metabolic disorders. They are emerging as a novel regulatory layer in adipogenesis and lipid metabolism involved in the development of obesity
A number of key questions remain: i) While the studies discussed above have confirmed that circRNAs display altered expression patterns in adipose tissue and obese individuals, the cell types and tissue origin of circRNAs in obesity are not yet fully explored
Summary
Whole-genome sequencing studies reveal that our genome comprises approximately 3 to 3.2 billion base pairs of DNA, but merely 1–2% of those pairs correspond to the annotated exons of protein-coding genes. Inconsistent with the “central dogma of biology” that describes the flow of genetic information from gene to mRNA and to protein, ncRNAs are generally not further translated into proteins [5] They do not encode proteins, these RNA molecules can still be endowed with critical regulatory function and may help orchestrate a hidden layer of gene regulation networks [6]. Considerable attention has focused on circRNAs, which are distinguished from their linear counterparts by the unique structure of covalently closed continuous loop lacking 50 cap and 30 poly-adenylated tails [10] This feature makes circRNAs remarkably stable and resistant to degradation by exonuclease and RNases, they are proposed as new generation of predictive biomarkers and potential therapeutic targets for many diseases. The sections will discuss relevant literature in the field and highlight some of the key aspects of circRNAs and challenges ahead
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