Molecular Cell Biology, Institute for Developmental Biology and Neurobiology, Department of Biology, Johannes Gutenberg-University of Mainz, Anselm-Franz-von-Bentzelweg 3, 55128 Mainz, Germany.
Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University, Duesbergweg 6, 55128 Mainz, Germany.
J Cell Sci. 2018 May 1;131(9):jcs204750. doi: 10.1242/jcs.204750.
In the central nervous system, oligodendroglial expression of myelin basic protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly at the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (also known as p68) in a complex with mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with mRNA in the cell body and processes. Manipulation of the amount of DDX5 protein inversely affects the level of MBP. We present evidence that DDX5 is involved in post-transcriptional regulation of MBP protein synthesis, with implications for oligodendroglial development. In addition, knockdown of DDX5 results in an increased abundance of MBP isoforms containing exon 2 in immature oligodendrocytes, most likely by regulating alternative splicing of Our findings contribute to the understanding of the complex nature of MBP post-transcriptional control in immature oligodendrocytes where DDX5 appears to affect the abundance of MBP proteins via distinct but converging mechanisms.
在中枢神经系统中，少突胶质细胞中髓鞘碱性蛋白（MBP）的表达对于髓鞘的组装和结构至关重要。MBP 的合成在时空上受到严格调控，特别是在转录后水平。我们在少突胶质细胞中与 mRNA 形成复合物的 DEAD-box RNA 解旋酶 DDX5（也称为 p68）。DDX5 的表达在祖细胞和未成熟的少突胶质细胞中最高，在那里它定位于与细胞体和突起中的 mRNA 相关的细胞质核糖核蛋白（RNP）复合物的异质群体中。DDX5 蛋白量的改变会反式影响 MBP 的水平。我们提出的证据表明，DDX5 参与 MBP 蛋白合成的转录后调控，这对少突胶质细胞的发育有影响。此外，DDX5 的敲低会导致不成熟少突胶质细胞中包含外显子 2 的 MBP 同工型的丰度增加，这很可能是通过调节 mRNA 的选择性剪接来实现的。我们的发现有助于理解不成熟少突胶质细胞中 MBP 转录后调控的复杂性质，其中 DDX5 似乎通过不同但趋同的机制影响 MBP 蛋白的丰度。
