Regulation by 3′-Untranslated Regions

Abstract

3′-untranslated regions (3′-UTRs) are the noncoding parts of mRNAs. Compared to yeast, in humans, median 3′-UTR length has expanded approximately tenfold alongside an increased generation of alternative 3′-UTR isoforms. In contrast, the number of coding genes, as well as coding region length, has remained similar. This suggests an important role for 3′-UTRs in the biology of higher organisms. 3′-UTRs are best known to regulate diverse fates of mRNAs, including degradation, translation, and localization, but they can also function like long noncoding or small RNAs, as has been shown for whole 3′-UTRs as well as for cleaved fragments. Furthermore, 3′-UTRs determine the fate of proteins through the regulation of protein–protein interactions. They facilitate cotranslational protein complex formation, which establishes a role for 3′-UTRs as evolved eukaryotic operons. Whereas bacterial operons promote the interaction of two subunits, 3′-UTRs enable the formation of protein complexes with diverse compositions. All of these 3′-UTR functions are accomplished by effector proteins that are recruited by RNA-binding proteins that bind to 3′-UTR cis-elements. In summary, 3′-UTRs seem to be major players in gene regulation that enable local functions, compartmentalization, and cooperativity, which makes them important tools for the regulation of phenotypic diversity of higher organisms.