As noted above, regulatory mutations have been identified in the 3′ UTRs of mRNAs, such as those underlying Tourette's syndrome [115] and muscular hypertrophy in sheep [116], which appear to involve gain- or loss-of-function of miRNA binding sites. Interestingly, however, a number of other reported 3′ UTR mutations do not appear to act in cis to regulate the expression of the associated mRNA, as is normally assumed, but rather in trans as ncRNAs. For example the 3′ UTR of prohibitin (in the absence of the associated protein-coding sequences) can inhibit cell cycle progression in one complementation group of breast cancer–derived cells that is characterized by naturally occurring mutations in the 3′ UTR, indicating that these sequences are in fact functioning, in part, as trans-acting ncRNAs [163],[164]. Similarly, the oogenesis defect observed in Drosophila oskar null mutants is rescued by the oskar 3′ UTR alone [165].
