Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes.
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.
Lau
Pierre
P
Division of Intramural Research, National Institute of Neurological Disorders and Stroke-National Institutes of Health, Bethesda, Maryland 20892-4479, USA.
Verrier
Jonathan D
JD
Nielsen
Joseph A
JA
Johnson
Kory R
KR
Notterpek
Lucia
L
Hudson
Lynn D
LD
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D019295:Computational Biology; D005699:Galactosylceramides / Q000378:metabolism; D005732:Gangliosides / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis / Q000379:methods; D009185:Myelin Proteins / Q000378:metabolism; D017711:Nonlinear Dynamics; D009836:Oligodendroglia / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000166:cytology; D014162:Transfection / Q000379:methods
D015703:Antigens, CD; D005699:Galactosylceramides; D005732:Gangliosides; D035683:MicroRNAs; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; C062875:ganglioside A2B5; D049452:Green Fluorescent Proteins