The Diverse Functions of IMP2/IGF2BP2 in Metabolism

核糖核酸 癌变 细胞生物学 RNA结合蛋白 生物 PI3K/AKT/mTOR通路 基因 遗传学 信号转导
作者
Ning Dai
出处
期刊:Trends in Endocrinology and Metabolism [Elsevier BV]
卷期号:31 (9): 670-679 被引量:82
标识
DOI:10.1016/j.tem.2020.05.007
摘要

The phosphorylation of IMPs by mTOR is critical for post-transcriptional gene expression regulation to coordinate cellular function and nutrient metabolism. IMP2 is a human T2D associated gene with impaired insulin secretion. The causal SNP in the second intron of IMP2 is an expression quantitative trait locus (eQTL) of IMP2 mRNA in islets. IMP2 deficient mice have better metabolic traits, such as improved glucose tolerance, improved insulin sensitivity, and are long-lived, although their islets secrete less insulin than those of control animals. The studies of tissue-specific IMP2-knockout mice demonstrate that IMP2 has critical roles in multiple tissues, such as brown fat, islets, liver, and adult muscle. IMP2 consistently governs fatty acid oxidation through post-transcriptional gene expression regulation across tissues. The human insulin-like growth factor 2 (IGF2) mRNA binding protein family (IMPs/IGF2BPs) is involved in a spectrum of biological processes, including development, tumorigenesis, and stemness. IMPs play a major role in post-transcriptional regulation of RNAs through the ribonucleoprotein complex (RNP). They have emerged as direct mammalian target of rapamycin (mTOR) substrates that coordinate nutrient stimulation and RNA life cycle control. IMP2 is a human type 2 diabetes (T2D) gene associated with impaired insulin secretion. Recently, using murine models, the substantial progress in understanding disease mechanisms has highlighted the significance of IMP2 in metabolism. This new knowledge may have the potential for therapeutic benefit. The human insulin-like growth factor 2 (IGF2) mRNA binding protein family (IMPs/IGF2BPs) is involved in a spectrum of biological processes, including development, tumorigenesis, and stemness. IMPs play a major role in post-transcriptional regulation of RNAs through the ribonucleoprotein complex (RNP). They have emerged as direct mammalian target of rapamycin (mTOR) substrates that coordinate nutrient stimulation and RNA life cycle control. IMP2 is a human type 2 diabetes (T2D) gene associated with impaired insulin secretion. Recently, using murine models, the substantial progress in understanding disease mechanisms has highlighted the significance of IMP2 in metabolism. This new knowledge may have the potential for therapeutic benefit. an approach used in human genetics to associate specific genetic variations with particular diseases. The method involves scanning the genomes of many different people and looking for genetic markers that can be used to predict the presence of a disease. Once such genetic markers are identified, they can be used to understand how genes contribute to the disease and develop better prevention and treatment strategies. the control of gene expression at the RNA level, therefore between the transcription and the translation of the gene. It contributes substantially to gene expression regulation across cell types. a complex formed between RNA and RNA-binding proteins. RNP granules are a highly diverse group of compartments, including stress granules, processing bodies, and exosomes in somatic cells. RNP granules have been shown to have particular importance in cells where post-transcriptional regulation is of vital importance. (single-nucleotide polymorphisms) are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a ‘nucleotide.’ For example, an SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. a metabolic disease in which a person’s body still produces insulin but is unable to use it effectively, which affects the way the body processes glucose.
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