A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis

Ngan Vo, Matthew E. Klein, Olga Varlamova, David M. Keller, Tadashi Yamamoto, Richard H. Goodman, Soren Impey

Research output: Contribution to journalArticle

633 Scopus citations

Abstract

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 neunte 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.

Original languageEnglish (US)
Pages (from-to)16426-16431
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005

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Keywords

  • MicroRNA
  • Neurite
  • Neurotrophin
  • Plasticity
  • Transcription

ASJC Scopus subject areas

  • General

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