REST and miRNAs Provide Double Negative Feedback

Mutations in huntingtin disrupt its interactions with REST, enabling repression of neuronal genes and contributing to Huntington's disease (HD). Among the genes inhibited by REST are several miRNAs — small, noncoding RNAs that inhibit translation by binding to complementary sequences in regulatory regions of mRNA. Packer et al. found that the levels of several miRNAs decreased as HD progressed. Of these, miR-9 and miR-9* had upstream regulatory regions that enabled repression by REST.

Interestingly, regulatory regions of REST and its cofactor CoREST have complementary sequences targeted by miR-9 and miR-9*, and miR-9 reduced expression of REST, while miR-9* targeted CoREST.

These molecules apparently form a double negative feedback loop, which is likely important for precise regulation of cell fate commitment.-Society for Neuroscience