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The Journal of Neuroscience, November 5, 2008, 28(45):11720-11730; doi:10.1523/JNEUROSCI.1932-08.2008

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Cellular/Molecular
Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes

Pierre Lau,¹ Jonathan D. Verrier,³ Joseph A. Nielsen,¹ Kory R. Johnson,² Lucia Notterpek,³ and Lynn D. Hudson¹

¹Section of Developmental Genetics and ²Bioinformatics Neuroscience Group, Information Technology Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892-4479, and ³Department of Neuroscience, McKnight Brain Institute of the University of Florida, Gainesville, Florida 32610-0244

Correspondence should be addressed to Lynn D. Hudson, Section of Developmental Genetics, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-0166. Email: hudsonl1{at}od.nih.gov

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.

Key words: microRNA; posttranscriptional regulation; oligodendrocyte; PMP22; myelin; glia

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Received Sept. 26, 2008; accepted Oct. 1, 2008.

Correspondence should be addressed to Lynn D. Hudson, Section of Developmental Genetics, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-0166. Email: hudsonl1{at}od.nih.gov

Related articles in J. Neurosci.:

Micromanaging Oligodendrocyte Differentiation by Noncoding RNA: Toward a Better Understanding of the Lineage Commitment Process

James Butcher, Houssein Abdou, Katy Morin, and Yubing Liu
J. Neurosci. 2009 29: 5365-5366. [Full Text]  

This article has been cited by other articles:

				J. Butcher, H. Abdou, K. Morin, and Y. Liu Micromanaging Oligodendrocyte Differentiation by Noncoding RNA: Toward a Better Understanding of the Lineage Commitment Process J. Neurosci., April 29, 2009; 29(17): 5365 - 5366. [Full Text] [PDF]

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