Poly C Binding Protein 2 dependent nuclear retention of the utrophin-A mRNA in C2C12 cells

Upregulation of utrophin, the autosomal homologue of dystrophin, can compensate dystrophin deficiency in Duchenne Muscular Dystrophy (DMD) although the therapeutic success is yet to be achieved. The present study has identified Poly (C) binding protein 2 (PCBP2) as a post-transcriptional suppresser for the expression of utrophin-A, the muscle-specific utrophin isoform. This study confirms nuclear retention of utrophin-A mRNA in C2C12 cells, which is mediated by PCBP2. Further investigation demonstrates PCBP2-dependent nuclear retention of follistatin mRNA as well. Its involvement in nuclear retention of mRNA sheds light on a novel function of PCBP2 that makes utrophin-A mRNA less available in cytosol. PCBP2, therefore, may be a target to de-repress utrophin-A expression in DMD.

肌养蛋白（utrophin）作为抗肌萎缩蛋白（dystrophin）的常染色体同源物，其表达上调可补偿杜氏肌营养不良症（Duchenne Muscular Dystrophy, DMD）中的抗肌萎缩蛋白缺陷，尽管目前尚未实现治疗层面的成功。本研究鉴定出聚胞嘧啶结合蛋白2（Poly (C) binding protein 2, PCBP2）为肌特异性肌养蛋白亚型A（utrophin-A）表达的转录后抑制因子。本研究证实，C2C12细胞中肌养蛋白亚型A mRNA的细胞核滞留现象由PCBP2介导。进一步实验表明，PCBP2同样可介导卵泡抑素mRNA的细胞核滞留。PCBP2参与mRNA细胞核滞留这一发现，揭示了该蛋白的全新生物学功能：其可降低胞质内肌养蛋白亚型A mRNA的可及性。因此，PCBP2或可作为杜氏肌营养不良症中解除肌养蛋白亚型A表达抑制的潜在治疗靶点。