Brief Communications The Bifunctional microRNAmiR-9/miR-9 * Regulates REST and CoREST and Is Downregulated in Huntington’s Disease

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 geneexpression. In thiswork,we found that levels of severalmicroRNAs (miRNAs)withupstreamRE1sites aredecreased inHD 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. Key words:miRNA; REST; Huntington’s disease; cortex; coordination; RNA interferenc