Skeletal 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-specific Hnrnpu knockout (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 link Hnrnpu with the balance between anabolic signaling, cellular and metabolic stress, and physiological growth.

骨骼肌具有出色的能力来响应营养输入，功能利用，全身性疾病和年龄的变化而调节其质量。这是通过协调转录和转录后网络以及信号级联来实现的，从而使合成代谢和分解代谢过程与能量和营养物质的利用达到平衡。可变剪接调节这些信令网络的程度尚不确定。在这里，我们研究了RNA结合蛋白hnRNP-U在基因表达和剪接以及调节骨骼肌肥大性生长的信号传导过程中的作用。肌肉特有的汉普基因敲除（mKO）小鼠会发展成年发作的肌病，其特征在于糖酵解肌肉的选择性萎缩，Akt的组成性激活，细胞和代谢应激基因表达的增加以及代谢和信号转导基因的表达和剪接的变化。这些发现将Hnrnpu与合成代谢信号，细胞和代谢应激以及生理生长之间的平衡联系起来。