Communication Is Key: 5'-3' Interactions that Regulate mRNA Translation and Turnover

Most eukaryotic mRNAs maintain a 5' cap structure and 3' poly(A) tail, cis-acting elements that are often separated by thousands of nucleotides. Nevertheless, multiple paradigms exist where mRNA 5' and 3' termini interact with each other in order to regulate mRNA translation and turnover. mRNAs recruit translation initiation factors to their termini, which in turn physically interact with each other. This physical bridging of the mRNA termini is known as the "closed loop" model, with years of genetic and biochemical evidence supporting the functional synergy between the 5' cap and 3' poly(A) tail to enhance mRNA translation initiation. However, a number of examples exist of "non-canonical" 5'-3' communication for cellular and viral RNAs that lack 5' cap structures and/or poly(A) tails. Moreover, in several contexts, mRNA 5'-3' communication can function to repress translation. Overall, we detail how various mRNA 5'-3' interactions play important roles in posttranscriptional regulation, wherein depending on the protein factors involved can result in translational stimulation or repression.