Almost all cells use mRNA localization to establish spatial control of protein synthesis. One of the best-studied examples is the targeting and anchoring of mRNAs encoding secreted, organellar, and membrane-bound proteins to the surface of the endoplasmic reticulum (ER). In this review, we provide a historical perspective on the research that elucidated the canonical protein-mediated targeting of nascent-chain ribosome mRNA complexes to the surface of the ER. We then discuss subsequent studies which provided concrete evidence that a subpopulation of mRNAs utilize a translation-independent mechanism to localize to the surface of this organelle. This alternative mechanism operates alongside the signal recognition particle (SRP) mediated co-translational targeting pathway to promote proper mRNA localization to the ER. Recent work has uncovered trans-acting factors, such as the mRNA receptor p180, and cis-acting elements, such as transmembrane domain coding regions, that are responsible for this alternative mRNA localization process. Furthermore, some unanticipated observations have raised the possibility that this alternative pathway may be conserved from bacteria to mammalian cells.
© 2014 John Wiley & Sons, Ltd.