The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease

Packer, Amy N., Xing, Yi, Harper, Scott Q., Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612 and Davidson, Beverley L. 2008. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. Journal of Neuroscience 28 (53) , pp. 14341-14346. 10.1523/JNEUROSCI.2390-08.2008

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Abstract

The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression. In this work, we found that levels of several microRNAs (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to healthy controls. Interestingly, one of these, the bifunctional brain enriched miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	miRNA; REST; Huntington's disease; cortex; coordination; RNA interference
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 26/02/2014).
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date of First Compliant Deposit:	30 March 2016
Last Modified:	03 May 2023 15:14
URI:	https://orca.cardiff.ac.uk/id/eprint/28860

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