A molecular mechanism for mRNA trafficking in neuronal dendrites

Shan, Jianguo, Munro, Trent P., Barbarese, Elisa, Carson, John H. and Smith, Ross (2003) A molecular mechanism for mRNA trafficking in neuronal dendrites. Journal of Neuroscience, 23 26: 8859-8866.

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Author Shan, Jianguo
Munro, Trent P.
Barbarese, Elisa
Carson, John H.
Smith, Ross
Title A molecular mechanism for mRNA trafficking in neuronal dendrites
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2003-10-01
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 23
Issue 26
Start page 8859
End page 8866
Total pages 8
Place of publication New York, USA
Publisher Society for Neuroscience
Collection year 2003
Language eng
Subject C1
270106 Cell Development (incl. Cell Division and Apoptosis)
250503 Characterisation of Macromolecules
250302 Biological and Medical Chemistry
780105 Biological sciences
270107 Cell Neurochemistry
270199 Biochemistry and Cell Biology not elsewhere classified
0601 Biochemistry and Cell Biology
Abstract Specific neuronal mRNAs are localized in dendrites, often concentrated in dendritic spines and spine synapses, where they are translated. The molecular mechanism of localization is mostly unknown. Here we have explored the roles of A2 response element (A2RE), a cis-acting signal for oligodendrocyte RNA trafficking, and its cognate trans-acting factor, heterogeneous nuclear ribonucleoprotein ( hnRNP) A2, in neurons. Fluorescently labeled chimeric RNAs containing A2RE were microinjected into hippocampal neurons, and RNA transport followed using confocal laser scanning microscopy. These RNA molecules, but not RNA lacking the A2RE sequence, were transported in granules to the distal neurites. hnRNP A2 protein was implicated as the cognate trans-acting factor: it was colocalized with RNA in cytoplasmic granules, and RNA trafficking in neurites was compromised by A2RE mutations that abrogate hnRNP A2 binding. Coinjection of antibodies to hnRNP A2 halved the number of trafficking cells, and treatment of neurons with antisense oligonucleotides also disrupted A2RE - RNA transport. Colchicine inhibited trafficking, whereas cells treated with cytochalasin were unaffected, implicating involvement of microtubules rather than microfilaments. A2RE-like sequences are found in a subset of dendritically localized mRNAs, which, together with these results, suggests that a molecular mechanism based on this cis-acting sequence may contribute to dendritic RNA localization.
Keyword Neurosciences
RNA trafficking
RNA localization
Neuronal dendrites
Hippocampal neurons
Confocal microscopy
Local protein-synthesis
Synaptic activation causes
Targeting element
Hnrnp A2
Living neurons
Growth cone
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 01:22:00 EST