Abstract
Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis. Altered insulin system is associated with major pathological conditions like diabetes and cancer. The mRNAs encoding for these ligands and their receptors are posttranscriptionally controlled by three major groups of regulators; (i) alternative splicing regulatory factors; (ii) turnover and translation regulator RNA-binding proteins (TTR-RBPs); and (iii) non-coding RNAs including miRNAs and long non-coding RNAs (lncRNAs). In this review, we discuss the influence of these regulators on alternative splicing, mRNA stability and translation. Due to the pathological impacts of insulin system, we also discussed the possibilities of discovering new potential regulators which will improve understanding of insulin system and associated diseases.
Highlights
Diabetes is one of the most common diseases in the United States accounting for about 25 million individuals and the number is expected to reach 40 million by 2050 [1]
insulin receptors (IR), insulin-like growth factors (IGFs), and insulin-like growth factor receptors (IGFR) is regulated at the posttranscriptional levels by the trans-acting factors of splicing regulatory RNA-binding proteins (RBPs), turnover and translation regulator RNA-binding proteins (TTR-RBPs), and non-coding RNAs including microRNAs and long non-coding RNAs
Diabetes could be an outcome of deregulated expression of the insulin system including insulin, IR, IGF, and IGFR [86]
Summary
Diabetes is one of the most common diseases in the United States accounting for about 25 million individuals and the number is expected to reach 40 million by 2050 [1]. IR, IGF, and IGFR is regulated at the posttranscriptional levels by the trans-acting factors of splicing regulatory RNA-binding proteins (RBPs), turnover and translation regulator RNA-binding proteins (TTR-RBPs), and non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These factors mainly regulate pre-mRNA alternative splicing and mRNA stability and translation. LncRNAs are not yet directly involved in posttranscriptional regulation of insulin system, HI-LNC25 affects pancreatic β-cells development; H19 regulates IGF-1R through miR-675-3p, while Airn was recently reported to regulate IGF-2R transcription [25,26,27]. We will focus on posttranscriptional regulation of insulin, IGFs and their receptors (IR and IGFR) by splicing regulatory RNA binding proteins, TTR-RBPs, and non-coding RNAs
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