Transcription profiling of rat oligodendrocyres to identify dynamically regulated microRNA and mRNA Networks

MicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -“microRNAome” - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3’ untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome. Experiment Overall Design: Flow cytometry was used to isolate single A2B5+ and single GalC+ oligodedrocytes from postnatal day 7 rat whole brain. 4 biological replicates were obtained for each group using a pooled litter of 10 pups per biological replicate