Muscle Developmental Defects in Heterogeneous Nuclear Ribonucleoprotein A1 Knockout Mice

Transcriptome analysis of total RNA samples from heart tissue of knockout mice Alternative splicing is the main mechanism to increase protein diversity from an mRNA. Heterogeneous ribonucleoprotein (hnRNP) family members are vital regulators of alternative splicing. The hnRNP A1 is the most well-known protein in this family, but its role in embryonic development is not well understood. We generated hnRNP A1 knockout mice to study the function of hnRNP A1 in vivo. The hnRNP A1-depleted mice showed embryonic lethality because of muscle developmental defects. In a previous study, cellular hnRNP A2/B1 was reported to be capable of compensating for the expression of hnRNP A1. However, this phenomenon did not occur in the hnRNP A1 heterozygous mice in vivo. We demonstrated that hnRNP A1 regulated muscle-related genes expression and alternative splicing. In summary, our data demonstrated that hnRNP A1 plays a critical role in embryonic muscle development. Understanding the effects of hnRNP A1 in vivo may help to define the function of hnRNP A1 in alternative splicing. We analyzed total RNA from heart of knockout mice (3 males) using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.本研究针对敲除小鼠心脏组织的总RNA样本开展转录组分析。可变剪接是从信使RNA（mRNA）扩增蛋白质多样性的核心机制。异质性核糖核蛋白（heterogeneous ribonucleoprotein, hnRNP）家族成员是可变剪接的关键调控因子。hnRNP A1是该家族中研究最为广泛的蛋白，但其在胚胎发育中的作用尚未完全阐明。我们构建了hnRNP A1敲除小鼠以在体研究其生物学功能。hnRNP A1敲除小鼠因肌肉发育缺陷出现胚胎致死表型。既往研究报道，细胞内的hnRNP A2/B1可代偿hnRNP A1的表达功能，但该代偿现象在体内的hnRNP A1杂合子小鼠中并未出现。我们证实，hnRNP A1可调控肌肉相关基因的表达与可变剪接事件。综上，本研究数据表明hnRNP A1在胚胎肌肉发育中发挥关键作用。阐明hnRNP A1在体的生物学效应，有助于明确其在可变剪接调控中的功能。我们采用Affymetrix Mouse Exon 1.0 ST芯片平台，对3只雄性敲除小鼠的心脏总RNA进行了转录组分析。芯片数据通过Affymetrix Exon Array Computational Tool进行处理。本实验未设置技术重复。