Towards a molecular understanding of the 5'TOP motif in regulating translation of ribosomal mRNAs

Vertebrate cells have evolved a simple, yet elegant, mechanism for coordinated regulation of ribosome biogenesis mediated by the 5' terminal oligopyrimidine motif (5'TOP). This motif allows cells to rapidly adapt to changes in the environment by specifically modulating translation rate of mRNAs encoding the translation machinery. Here, we provide an overview of the origin of this motif, its characterization, and progress in identifying the key regulatory factors involved. We highlight challenges in the field of 5'TOP research, and discuss future approaches that we think will be able to resolve outstanding questions.