Emerging roles of RNA‐binding proteins in diabetes and their therapeutic potential in diabetic complications

Abstract

Diabetes is a debilitating health care problem affecting 422 million people around the world. Diabetic patients suffer from multisystemic complications that can cause mortality and morbidity. Recent advancements in high-throughput next-generation RNA-sequencing and computational algorithms led to the discovery of aberrant posttranscriptional gene regulatory programs in diabetes. However, very little is known about how these regulatory programs are mis-regulated in diabetes. RNA-binding proteins (RBPs) are important regulators of posttranscriptional RNA networks, which are also dysregulated in diabetes. Human genetic studies provide new evidence that polymorphisms and mutations in RBPs are linked to diabetes. Therefore, we will discuss the emerging roles of RBPs in abnormal posttranscriptional gene expression in diabetes. Questions that will be addressed are: Which posttranscriptional mechanisms are disrupted in diabetes? Which RBPs are responsible for such changes under diabetic conditions? How are RBPs altered in diabetes? How does dysregulation of RBPs contribute to diabetes? Can we target RBPs using RNA-based methods to restore gene expression profiles in diabetic patients? Studying the evolving roles of RBPs in diabetes is critical not only for a comprehensive understanding of diabetes pathogenesis but also to design RNA-based therapeutic approaches for diabetic complications. WIREs RNA 2018, 9:e1459. doi: 10.1002/wrna.1459 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing Translation > Translation Regulation.

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

“…Nutritional effects, which can contribute to the development of some NCDs, can alter levels of growth factors, hormones, and cellular receptors that regulate signaling pathways that control both transcriptional and translational gene expression [10]. These alterations regulating translation initiation can directly control gene expression levels, with neurological, endocrine, pulmonary, and cardiovascular functions commonly disrupted [11][12][13][14][15].…”

RNA Binding Motif 5 (RBM5) in the CNS—Moving Beyond Cancer to Harness RNA Splicing to Mitigate the Consequences of Brain Injury

“…A recent surge of disease-focused reviews have highlighted the emerging clinical interest for therapeutically targeting RBPs in the setting of: neurodegenerative diseases (Hofmann et al, 2019 ; Nussbacher et al, 2019 ), pain disorders (de la Pena and Campbell, 2018 ), cancer (Pereira et al, 2017 ), immunity (Turner and Díaz-Muñoz, 2018 ), diabetes (Nutter and Kuyumcu-Martinez, 2018 ), muscle wasting (Van Pelt et al, 2019 ), reproductive pathologies (Khalaj et al, 2017 ), cardiovascular disease (de Bruin et al, 2017 ), renal injury (Ignarski et al, 2019 ) and hepatic illness (Lee et al, 2020 ). Increased awareness of RBPs as targets has accelerated efforts to develop therapies that disrupt and/or modulate their activity.…”

mRNA Processing: An Emerging Frontier in the Regulation of Pancreatic β Cell Function

“…Many studies have focused on the mis-regulation of mRNAs and RBP function in the context of diabetic complications (adipose, liver, muscle, retina, etc. ), rather than specific changes in the β cells (Nutter and Kuyumcu-Martinez, 2018). In the pancreas, only a few groups have delved into the world of RNA regulation, often focusing on a single splicing target or RBP.…”