Dual role of the RNA helicase DDX5 in post-transcriptional regulation of Myelin Basic Protein in oligodendrocytes

Abstract

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 on the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (alias p68) in a complex with Mbp 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 Mbp mRNA in the cell body and processes. Manipulation of DDX5 protein amounts inversely affects levels of MBP protein. We present evidence that DDX5 is involved in post-transcriptional regulation of MBP protein synthesis, with implications for oligodendroglial development. In addition, DDX5 knockdown results in an increased abundance of MBP exon 2-positive isoforms in immature oligodendrocytes, most likely by regulating alternative splicing of Mbp. 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.