RNAs and RNA-Binding Proteins in Immuno-Metabolic Homeostasis and Diseases

Abstract

The increasing prevalence of worldwide obesity has emerged as a major risk factor for type 2 diabetes (T2D), hepatosteatosis, and cardiovascular disease. Accumulating evidence indicates that obesity has strong inflammatory underpinnings tightly linked to the development of metabolic diseases. However, the molecular mechanisms by which obesity induces aberrant inflammation associated with metabolic diseases are not yet clearly defined. Recently, RNAs have emerged as important regulators of stress responses and metabolism. RNAs are subject to changes in modification status, higher-order structure, and cellular localization; all of which could affect the affinity for RNA-binding proteins (RBPs) and thereby modify the RNA-RBP networks. Proper regulation and management of RNA characteristics are fundamental to cellular and organismal homeostasis, as well as paramount to health. Identification of multiple single nucleotide polymorphisms (SNPs) within loci of fat mass- and obesity-associated protein (FTO) gene, an RNA demethylase, through genome-wide association studies (GWAS) of T2D, and functional assessments of FTO in mice, support the concept that disruption in RNA modifications leads to the development of human diseases including obesity and metabolic disorder. In obesity, dynamic alterations in modification and localization of RNAs appear to modulate the RNA-RBP networks and activate proinflammatory RBPs, such as double-stranded RNA (dsRNA)-dependent protein kinase (PKR), Toll-like receptor (TLR) 3 and TLR7, and RNA silencing machinery. These changes induce aberrant inflammation and the development of metabolic diseases. This review will describe the current understanding of the underlying causes of these common and altered characteristics of RNA-RBP networks which will pave the way for developing novel approaches to tackle the pandemic issue of obesity.

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

“…We have summarized the classical as well as emerging hallmark functions of RBPs in Figure 1. Given their widespread impact on gene expression and signaling networks, mutations or defects in the expression or localization of RBPs can cause a broad range of diseases, e.g., neurodegeneration, obesity, hypertension, and cancer [55,[89][90][91][92][93][94][95][96]. In the next paragraph, we will highlight selected examples of RBPs that have been shown to contribute to the malignancy of oral cancer, especially its metastatic features.…”

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

“…This is probably what occurs in asymptomatic individuals who can establish an effective response against SARS-CoV-2 (9, 141). However, in several viruses, viral proteins can modulate the production of this type of IFN, impairing the generation of an effective antiviral response (141,143,146,147). Li et al (148) conducted an in vitro experiment that revealed a strong capacity of ORF6, ORF8, and nucleocapsid proteins of SARS-CoV-2 to inhibit IFN-b and NF-kB activity, in addition to genes containing interferonstimulated response elements (ISREs), suggesting that the virus has an important IFN antagonist activity.…”

Role of long non‐coding RNAs in adipogenesis: State of the art and implications in obesity and obesity‐associated diseases

“…Among the non‐coding RNAs, it is possible to distinguish two subclasses: small non‐coding RNAs, molecules smaller than 200 bp, and lncRNAs, defined as non‐coding RNA molecules longer than 200 bp 22 . LncRNAs are poorly conserved, frequently unstable, and/or sometimes present in few copies, and new biological roles have emerged for some lncRNAs 23–25 . In order to facilitate the reader through this mounting evidence in different models, the lncRNAs reported in this work are listed for their homology as summarized in Table S1.…”