The transcriptome of mouse central nervous system myelin.

Ramona B. Jung,Vijay K. Tiwari,Hauke B. Werner,Sudhir Thakurela,Angela Garding,Robin White,Sandra Goebbels,Christina Müller

doi:10.1038/srep25828

Abstract

Rapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting a highly selective incorporation of mRNAs into the myelin compartment. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months were minor. We suggest that this transcript pool enables myelin turnover and the local adaptation of individual pre-existing myelin sheaths.

Highlights

Purified myelin compared to brain lysates, along with transcripts encoding the unrelated myelin-oligodendrocyte basic protein (MOBP) and ferritin heavy chain (FTH1)[6]
When comparing all moderately and highly abundant transcripts with mRNAs enriched in myelin compared to both cerebellum and cortex (n = 1020) we found that most myelin-enriched transcripts are expressed at all stages of oligodendroglial maturation (n = 745) (Fig. 3D)
We report that CNS myelin comprises an unexpectedly large number of mRNAs, with transcripts of >13000 mRNAs present at least at a moderate abundance level; a surprising finding when considering that only very few mRNAs have been previously recognized in myelin using a small-scale approach[6]

Summary

Introduction

Purified myelin compared to brain lysates, along with transcripts encoding the unrelated myelin-oligodendrocyte basic protein (MOBP) and ferritin heavy chain (FTH1)[6]. Considering that the turnover and adaptation of myelin require the availability and selective incorporation of many more proteins into the future myelin sheath we sought to systematically determine by RNA-Sequencing (RNA-Seq) the mRNAs present in CNS myelin. We find that adult CNS myelin comprises an unexpectedly large number of mRNAs. Developmentally, the myelin transcriptome reaches maturity by six months of age. According to functional genomic analysis, myelin is enriched for mRNAs encoding myelin proteins, components of the translational machinery, and molecules required for protein transport and localization

Methods

Results

Conclusion