A deep dive into functional ribosome specialization

Ribosome specialization, whereby ribosomes of distinct composition translate different sets of mRNAs, is a concept that has garnered both wide-spread excitement and skepticism from the translation field. The controversy is rooted in experimental challenges, which make rigorous controls difficult and not obvious to the nonexpert. In addition, considerations of translation mechanisms and ribosome homeostasis also suggest heterogeneity to be limited, fueling doubt. Lastly, the mechanisms by which heterogeneity can lead to specialization are often challenging to imagine and not spelled out. In this perspective, we define ribosome heterogeneity and specialization, use examples to examine both the technical challenges and potential solutions. We then consider the mechanism-based challenges with the goal of proposing biologically relevant circumstances where ribosome specialization might exist and how it might affect translation in an mRNA-specific manner. It is hoped that this article will help resolve the controversy around the subject, in addition to providing a guide for scientists entering the field, so they can concentrate their efforts fruitfully and rigorously.