SncRNA715 Inhibits Schwann Cell Myelin Basic Protein Synthesis.

Christina Müller,Nina M Hochhaus,Xavier Fontana,Heiko J Luhmann,Robin White,Sven G Meuth

doi:10.1371/journal.pone.0136900

Abstract

Myelin basic proteins (MBP) are major constituents of the myelin sheath in the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS Mbp translation occurs locally at the axon-glial contact site in a neuronal activity-dependent manner. Recently we identified the small non-coding RNA 715 (sncRNA715) as a key inhibitor of Mbp translation during transport in oligodendrocytes. Mbp mRNA localization in Schwann cells has been observed, but has not been investigated in much detail. Here we could confirm translational repression of Mbp mRNA in Schwann cells. We show that sncRNA715 is expressed and its levels correlate inversely with MBP in cultured Schwann cells and in the sciatic nerve in vivo. Furthermore we could reduce MBP protein levels in cultured Schwann cells by increasing the levels of the inhibitory sncRNA715. Our findings suggest similarities in sncRNA715-mediated translational repression of Mbp mRNA in oligodendrocytes and Schwann cells.

Highlights

In the peripheral nervous system myelinating Schwann cells form a lipid-rich myelin membrane around axonal segments allowing saltatory conduction of action potentials
We initially addressed the questions if undifferentiated Schwann cells contain Mbp mRNA while lacking Myelin Basic Protein (MBP) protein, to assess if Mbp mRNA is translationally repressed in these cells as well
Reverse transcription and subsequent PCR (RT-PCR) with MBP-specific primers revealed the presence of Mbp mRNA in these cells similar to Oli-neu cells which we used as a positive control (Fig 1A) whereas a water control did not show any signal

Summary

Introduction

In the peripheral nervous system myelinating Schwann cells form a lipid-rich myelin membrane around axonal segments allowing saltatory conduction of action potentials. Proliferation, migration and myelination of Schwann cells is controlled by the neuronal EGF-receptor family protein Neuregulin 1 (NRG1) which binds to Schwann cell ErbB2/3 receptors and activates second messenger cascades [1,2,3,4,5] Upon this interaction myelination takes place very locally suggesting spatial and temporal regulatory mechanisms [6,7]. Schwann cell MBP controls these numbers by affecting the stability and turnover rate of SLI proteins such as Connexin-32 and Myelin Associated Glycoprotein (MAG). The expression of both proteins is inversely proportional to MBP in the sciatic nerve of shiverer mice [12]

Methods

Results

Conclusion