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A role for huntington disease protein in dendritic RNA granules.

A role for huntington disease protein in dendritic RNA granules.
A role for huntington disease protein in dendritic RNA granules.
Regulated transport and local translation of mRNA in neurons are critical for modulating synaptic strength, maintaining proper neural circuitry, and establishing long term memory. Neuronal RNA granules are ribonucleoprotein particles that serve to transport mRNA along microtubules and control local protein synthesis in response to synaptic activity. Studies suggest that neuronal RNA granules share similar structures and functions with somatic P-bodies. We recently reported that the Huntington disease protein huntingtin (Htt) associates with Argonaute (Ago) and localizes to cytoplasmic P-bodies, which serve as sites of mRNA storage, degradation, and small RNA-mediated gene silencing. Here we report that wild-type Htt associates with Ago2 and components of neuronal granules and co-traffics with mRNA in dendrites. Htt was found to co-localize with RNA containing the 3'-untranslated region sequence of known dendritically targeted mRNAs. Knockdown of Htt in neurons caused altered localization of mRNA. When tethered to a reporter construct, Htt down-regulated reporter gene expression in a manner dependent on Ago2, suggesting that Htt may function to repress translation of mRNAs during transport in neuronal granules.
gene silencing, neurodegeneration, p-body, rna silencing, rna transport, huntington disease, neuronal rna granules, post-transciptional gene silencing
0021-9258
13142-13153
Savas, Jeffrey N.
47dcb2d3-9d00-4a94-a7ba-f46dd9b00b5a
Ma, Bin
ba3617eb-138f-496f-9d5e-c7d53dd4b9fa
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Culver, Brady P.
6c40fed4-9518-4706-a253-a3e6d224b933
Restituito, Sophie
c88e7b8e-a33b-4331-8139-aa15fbf6b336
Wu, Ligang
078c4cdc-89e7-4036-bdbc-75cdf00a97ec
Belasco, Joel G.
cde9bf40-3bea-4c82-b050-9bddf5f650da
Chao, Moses V.
823c00e2-9f32-4a7b-a2c4-76e7c1fbf83d
Tanese, Naoko
90840470-f1f7-4e55-bc35-8d9bf83b3d96
Savas, Jeffrey N.
47dcb2d3-9d00-4a94-a7ba-f46dd9b00b5a
Ma, Bin
ba3617eb-138f-496f-9d5e-c7d53dd4b9fa
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Culver, Brady P.
6c40fed4-9518-4706-a253-a3e6d224b933
Restituito, Sophie
c88e7b8e-a33b-4331-8139-aa15fbf6b336
Wu, Ligang
078c4cdc-89e7-4036-bdbc-75cdf00a97ec
Belasco, Joel G.
cde9bf40-3bea-4c82-b050-9bddf5f650da
Chao, Moses V.
823c00e2-9f32-4a7b-a2c4-76e7c1fbf83d
Tanese, Naoko
90840470-f1f7-4e55-bc35-8d9bf83b3d96

Savas, Jeffrey N., Ma, Bin, Deinhardt, Katrin, Culver, Brady P., Restituito, Sophie, Wu, Ligang, Belasco, Joel G., Chao, Moses V. and Tanese, Naoko (2010) A role for huntington disease protein in dendritic RNA granules. The Journal of Biological Chemistry, 285 (17), 13142-13153. (doi:10.1074/jbc.M110.114561). (PMID:20185826)

Record type: Article

Abstract

Regulated transport and local translation of mRNA in neurons are critical for modulating synaptic strength, maintaining proper neural circuitry, and establishing long term memory. Neuronal RNA granules are ribonucleoprotein particles that serve to transport mRNA along microtubules and control local protein synthesis in response to synaptic activity. Studies suggest that neuronal RNA granules share similar structures and functions with somatic P-bodies. We recently reported that the Huntington disease protein huntingtin (Htt) associates with Argonaute (Ago) and localizes to cytoplasmic P-bodies, which serve as sites of mRNA storage, degradation, and small RNA-mediated gene silencing. Here we report that wild-type Htt associates with Ago2 and components of neuronal granules and co-traffics with mRNA in dendrites. Htt was found to co-localize with RNA containing the 3'-untranslated region sequence of known dendritically targeted mRNAs. Knockdown of Htt in neurons caused altered localization of mRNA. When tethered to a reporter construct, Htt down-regulated reporter gene expression in a manner dependent on Ago2, suggesting that Htt may function to repress translation of mRNAs during transport in neuronal granules.

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More information

e-pub ahead of print date: 25 February 2010
Published date: 23 April 2010
Keywords: gene silencing, neurodegeneration, p-body, rna silencing, rna transport, huntington disease, neuronal rna granules, post-transciptional gene silencing
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 349687
URI: http://eprints.soton.ac.uk/id/eprint/349687
ISSN: 0021-9258
PURE UUID: d6196568-e069-4265-8954-416228a6f67b
ORCID for Katrin Deinhardt: ORCID iD orcid.org/0000-0002-6473-5298

Catalogue record

Date deposited: 11 Mar 2013 11:23
Last modified: 20 Jul 2019 00:40

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