文章基本信息

标题：Adult-Onset Myopathy with Constitutive Activation of Akt following the Loss of hnRNP-U
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作者：Debalina Bagchi ; Benjamin D. Mason ; Kodilichi Baldino 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：7
页码：1-24
DOI：10.1016/j.isci.2020.101319
语种：English
出版社：Elsevier
摘要：SummarySkeletal muscle has the remarkable ability to modulate its mass in response to changes in nutritional input, functional utilization, systemic disease, and age. This is achieved by the coordination of transcriptional and post-transcriptional networks and the signaling cascades balancing anabolic and catabolic processes with energy and nutrient availability. The extent to which alternative splicing regulates these signaling networks is uncertain. Here we investigate the role of the RNA-binding protein hnRNP-U on the expression and splicing of genes and the signaling processes regulating skeletal muscle hypertrophic growth. Muscle-specificHnrnpuknockout (mKO) mice develop an adult-onset myopathy characterized by the selective atrophy of glycolytic muscle, the constitutive activation of Akt, increases in cellular and metabolic stress gene expression, and changes in the expression and splicing of metabolic and signal transduction genes. These findings linkHnrnpuwith the balance between anabolic signaling, cellular and metabolic stress, and physiological growth.Graphical AbstractDisplay OmittedHighlights•HnrnpumKO mice develop adult-onset myopathy with selective glycolytic muscle atrophy•Akt is constitutively active in the atrophied muscles ofHnrnpumKO mice•Hnrnpumutants show altered gene expression and alternative splicing patterns•Induction of genes associated with cellular and metabolic stressCellular Physiology; Molecular Genetics; Molecular Physiology