期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 45, 页码 11720-11730出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1932-08.2008
关键词
microRNA; posttranscriptional regulation; oligodendrocyte; PMP22; myelin; glia
资金
- National Institute of Neurological Disorders and Stroke
- Muscular Dystrophy Association
- McKnight Brain Institute
- Joshua Benjamin Weitzel Fund for Developmental Neurobiology
MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile ( microRNAome) contains 43 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 downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3' untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
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