A trans-acting function for mRNA sequences, both coding and noncoding, may be more general that expected. For example, the introduction of cancer-associated silent point-mutations in p53 mRNA alters its binding to the protein Mdm2, which in turn alters p53 expression and function [166]. The 3′ UTRs of troponin I, tropomyosin, and α-cardiac actin have been shown to reactivate muscle-specific promoters in a differentiation-defective myoblast mutant, enhance the differentiation of wild-type muscle cells, and suppress the proliferation of fibroblasts independently of their normally associated protein-coding sequences [167]. Similarly, the 3′ UTRs of tropomysin [168] and ribonucleotide reductase [169] can suppress tumour formation, and the 3′ UTR of the DM protein kinase gene, which is involved in myotonic dystrophy, inhibits the differentiation of C2C12 myoblasts [170]. Moreover, many 3′ UTRs in mouse appear to be expressed separately from their mRNAs in a developmentally regulated manner [171].
