Detection and Function of the Eukaryotic Vacant Ribosome

Upon transcription, most mRNAs associate with the small ribosomal subunit, after which a fully translating ribosome assembles. Under starvation or stress, however, this association is blocked and many mRNAs are instead sequestered with specific RNA-binding proteins into stress granules or other subcellular condensates. In contrast, much less attention has been paid to the fate of ribosomes under these same conditions. Ribosomes often remain fully assembled but unbound to mRNA, entering an inactive, dormant state. Dormancy is often supported by specific protein factors which protect them from degradation and facilitate reactivation once growth conditions improve. In this review, we highlight that dormant ribosome states are well defined in prokaryotes, in part because they possess distinct and experimentally tractable features, such as stable vacant 100S dimers. In eukaryotes, by contrast, analogous defining signatures are largely absent, making their discovery more indirect and method-dependent. We therefore focus on how evidence for eukaryotic dormant ribosomes has been assembled through multiple independent findings and how their interpretation depends critically on the experimental approaches used to study them.