An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons.
mRNA localization is an evolutionary conserved mechanism that underlies the establishment of cellular polarity and specialized cell functions. To identify mRNAs localized in subcellular compartments of developing neurons, we took an original approach that combines compartmentalized cultures of rat sympathetic neurons and sequential analysis of gene expression (SAGE). Unexpectedly, the most abundant transcript in axons was mRNA for myo-inositol monophosphatase-1 (Impa1), a key enzyme that regulates the inositol cycle and the main target of lithium in neurons. A novel localization element within the 3' untranslated region of Impa1 mRNA specifically targeted Impa1 transcript to sympathetic neuron axons and regulated local IMPA1 translation in response to nerve growth factor (NGF). Selective silencing of IMPA1 synthesis in axons decreased nuclear CREB activation and induced axonal degeneration. These results provide insights into mRNA transport in axons and reveal a new NGF-responsive localization element that directs the targeting and local translation of an axonal transcript.
Andreassi
Catia
C
Medical Research Council Laboratory for Molecular and Cell Biology, University College London, London, UK.
Zimmermann
Carola
C
Mitter
Richard
R
Fusco
Salvatore
S
De Vita
Serena
S
Devita
Serena
S
Saiardi
Adolfo
A
Riccio
Antonella
A
D020413:3' Untranslated Regions; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D013347:Subcellular Fractions / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014741:Video Recording
D020413:3' Untranslated Regions; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase