A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis.
MicroRNAs (miRNAs) regulate cellular fate by controlling the stability or translation of mRNA transcripts. Although the spatial and temporal patterning of miRNA expression is tightly controlled, little is known about signals that induce their expression nor mechanisms of their transcriptional regulation. Furthermore, few miRNA targets have been validated experimentally. The miRNA, miR132, was identified through a genome-wide screen as a target of the transcription factor, cAMP-response element binding protein (CREB). miR132 is enriched in neurons and, like many neuronal CREB targets, is highly induced by neurotrophins. Expression of miR132 in cortical neurons induced neurite outgrowth. Conversely, inhibition of miR132 function attenuated neuronal outgrowth. We provide evidence that miR132 regulates neuronal morphogenesis by decreasing levels of the GTPase-activating protein, p250GAP. These data reveal that a CREB-regulated miRNA regulates neuronal morphogenesis by responding to extrinsic trophic cues.
Vo
Ngan
N
Vollum Institute, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Klein
Matthew E
ME
Varlamova
Olga
O
Keller
David M
DM
Yamamoto
Tadashi
T
Goodman
Richard H
RH
Impey
Soren
S
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000502:physiology; D007438:Introns; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D016716:PC12 Cells; D051381:Rats; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D020690:GTPase-Activating Proteins; D035683:MicroRNAs