XB-ART-38389Exp Cell Res. August 15, 2008; 314 (14): 2618-33.
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.
PubMed ID: 18619591
PMC ID: PMC2702206
Article link: Exp Cell Res.
Grant support: R01 NS038698-05 NINDS NIH HHS , R01 NS038698-06 NINDS NIH HHS , R01 NS038698-07 NINDS NIH HHS , R01 NS38698 NINDS NIH HHS
Genes referenced: actl6a cdc42 rac1 rho rho.2 tuba4b