MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation.
MicroRNAs (miRNAs) are small RNAs with diverse regulatory roles. The miR-124 miRNA is expressed in neurons in the developing and adult nervous system. Here we show that overexpression of miR-124 in differentiating mouse P19 cells promotes neurite outgrowth, while blocking miR-124 function delays neurite outgrowth and decreases acetylated alpha-tubulin. Altered neurite outgrowth also was observed in mouse primary cortical neurons when miR-124 expression was increased, or when miR-124 function was blocked. In uncommitted P19 cells, miR-124 expression led to disruption of actin filaments and stabilization of microtubules. Expression of miR-124 also decreased Cdc42 protein and affected the subcellular localization of Rac1, suggesting that miR-124 may act in part via alterations to members of the Rho GTPase family. Furthermore, constitutively active Cdc42 or Rac1 attenuated neurite outgrowth promoted by miR-124. To obtain a broader perspective, we identified mRNAs downregulated by miR-124 in P19 cells using microarrays. mRNAs for proteins involved in cytoskeletal regulation were enriched among mRNAs downregulated by miR-124. A miR-124 variant with an additional 5' base failed to promote neurite outgrowth and downregulated substantially different mRNAs. These results indicate that miR-124 contributes to the control of neurite outgrowth during neuronal differentiation, possibly by regulation of the cytoskeleton.
Yu
Jenn-Yah
JY
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Chung
Kwan-Ho
KH
Deo
Monika
M
Thompson
Robert C
RC
Turner
David L
DL
D000107:Acetylation; D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014981:Xenopus; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D014404:Tubulin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein