The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

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.

Emerging roles of circular RNAs in systemic lupus erythematosus

“… 16 , 17 , 18 , 19 circRNA expression is also modulated by the regulation of circularization, which involves three main hypothetical models: lariat-driven circularization, in which the formation of a lariat structure brings the upstream splice acceptor and downstream donor into close proximity before splicing; intron-pairing-driven circularization, in which the inverted complementary repeat sequences combine into RNA double strands and are subjected to alternative splicing; and RNA binding protein (RBP)-mediated circularization, in which RBPs join the upstream and downstream flanking introns to facilitate pre-mRNA circularization back-splicing ( Figure 1 ). 13 , 20 , 21 , 22 The type of circRNAs generated depends mainly on the elements involved in the three hypothetical models and the splicing pattern.…”

Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions

“…The level of circRNAs varies in different tissues and according to cellular conditions [ 7 , 80 ]. Moreover, as outlined in the previous chapters, the expression of some circRNAs is altered under disease states [ 7 , 8 , 9 , 10 , 11 ], including diabetes [ 72 , 73 , 81 ]. Finally, some circRNAs are secreted in the extracellular space and are abundant in body fluids (blood, saliva, urine, cerebrospinal fluid) and are detectable in liquid biopsies [ 82 , 83 ].…”

“…Some of them are conserved between species (in particular between humans and mice), are tissue-specific, and modulate mRNA transcription, splicing, and translation, affecting diverse cellular processes [ 1 , 2 , 3 ]. Abnormal expression of circRNAs has been implicated in a wide range of human cancers [ 7 ], in metabolic dysfunction [ 8 , 9 ], and in cardiovascular diseases [ 10 , 11 ].…”

Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

“…Based on their biological function, ncRNAs can be classified into infrastructural and regulatory types. Infrastructural ncRNAs include ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs) and transfer RNAs (tRNAs) while regulatory ncRNAs are mainly represented by circular RNAs (circRNAs), long non coding RNAs (lncRNAs), microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) [ 5 ]. Although they do not encode proteins, ncRNAs are functionally active and contribute to the regulation of protein-coding gene expression [ 6 ] through different mechanisms including modification of chromatin structure, repressing/activating transcription and post-transcriptional regulation [ 3 , 7 ].…”