3′ UTRs Regulate Protein Functions by Providing a Nurturing Niche during Protein Synthesis

Abstract

Messenger RNAs (mRNAs) are the templates for protein synthesis as the coding region is translated into the amino acid sequence. mRNAs also contain 3′ untranslated regions (3′ UTRs) that harbor additional elements for the regulation of protein function. If the amino acid sequence of a protein is necessary and sufficient for its function, we call it 3′ UTR–independent. In contrast, functions that are accomplished by protein complexes whose formation requires the presence of a specific 3′ UTR are 3′ UTR–dependent protein functions. We showed that 3′ UTRs can regulate protein activity without affecting protein abundance, and alternative 3′ UTRs can diversify protein functions. We currently think that the regulation of protein function by 3′ UTRs is facilitated by the local environment at the site of protein synthesis, which we call the nurturing niche for nascent proteins. This niche is composed of the mRNA and the bound proteins that consist of RNA-binding proteins and recruited proteins. It enables the formation of specific protein complexes, as was shown for TIS granules, a recently discovered cytoplasmic membraneless organelle. This finding suggests that changing the niche for nascent proteins will alter protein activity and function, implying that cytoplasmic membraneless organelles can regulate protein function in a manner that is independent of protein abundance.