CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 48160 Derio, Bizkaia, Spain.
J Neurosci. 2012 Apr 4;32(14):4944-58. doi: 10.1523/JNEUROSCI.5868-11.2012.
An important prerequisite to myelination in peripheral nerves is the establishment of one-to-one relationships between axons and Schwann cells. This patterning event depends on immature Schwann cell proliferation, apoptosis, and morphogenesis, which are governed by coordinated changes in gene expression. Here, we found that the RNA-binding protein human antigen R (HuR) was highly expressed in immature Schwann cells, where genome-wide identification of its target mRNAs in vivo in mouse sciatic nerves using ribonomics showed an enrichment of functionally related genes regulating these processes. HuR coordinately regulated expression of several genes to promote proliferation, apoptosis, and morphogenesis in rat Schwann cells, in response to NRG1, TGFβ, and laminins, three major signals implicated in this patterning event. Strikingly, HuR also binds to several mRNAs encoding myelination-related proteins but, contrary to its typical function, negatively regulated their expression, likely to prevent ectopic myelination during development. These functions of HuR correlated with its abundance and subcellular localization, which were regulated by different signals in Schwann cells.
髓鞘形成在外周神经中的一个重要前提是轴突和施万细胞之间建立一一对应的关系。这种模式事件取决于未成熟施万细胞的增殖、凋亡和形态发生，这是由基因表达的协调变化所控制的。在这里，我们发现 RNA 结合蛋白人抗原 R (HuR) 在未成熟的施万细胞中高度表达，在体内使用核糖组学在小鼠坐骨神经中对其在体内的靶 mRNA 进行全基因组鉴定表明，功能相关基因的富集调节了这些过程。HuR 协调调节了几种基因的表达，以促进大鼠施万细胞的增殖、凋亡和形态发生，以响应 NRG1、TGFβ 和层粘连蛋白，这三种主要信号涉及到这种模式事件。引人注目的是，HuR 还与几个编码髓鞘形成相关蛋白的 mRNA 结合，但与它的典型功能相反，负调节它们的表达，可能是为了防止发育过程中的异位髓鞘形成。HuR 的这些功能与其丰度和亚细胞定位相关，这些定位受施万细胞中不同信号的调节。
