Finally, it is important to note that at least two other modes of regulation are likely to play key roles in expression of the nACh receptor β4 subunit gene (as well as other nACh receptor subunit genes). First, in addition to the cis-acting elements described thus far, chromatin remodeling most probably is critical for appropriate β4 gene expression. This is a relatively understudied area in terms of nACh receptor gene expression and is a focus of current research efforts. Second, post-transcriptional mechanisms are another level of control of nACh receptor expression, particularly in response to extracellular stimuli. One such mechanism may involve small 21-24 nucleotide long regulatory molecules, referred to as microRNAs (miRNAs) (Ambros, 2004). miRNAs are predicted to regulate the majority of mammalian protein-coding genes, typically by binding to complementary sites in the 3′-untranslated regions of target mRNAs and guiding them to an RNA-induced silencing complex (Kosik, 2006). Interestingly, a miRNA, miR-1, has been reported to target nACh receptors in C. elegans, leading to changes in nACh receptor properties (Simon et al., 2008). We are investigating whether miRNAs play a role in the expression of mammalian nACh receptor genes.
