Nuclear export and cytoplasmic maturation of eukaryotic ribosomes

In eukaryotic cells ribosomes are largely preassembled in the nucleolus. They are exported to the cytoplasm in a functionally inactive state due to the presence of trans‐acting factors that preclude their function, and the absence of critical ribosomal proteins. Consequently, the acquisition of functionality in the cytoplasm involves a series of remodeling events that release and recruit proteins. We have ordered the known steps of 60S maturation into a coherent pathway. Maturation is initiated by the ATPase Drg1. Subsequent assembly of the ribosome stalk is essential for the release of the subunit anti‐association factor Tif6. The ribosome stalk recruits elongation factors during translation. Our work suggests that during ribosome biogenesis, assembly of the stalk triggers a quasi‐functional check of the large subunit through the recruitment of the elongation factor‐like GTPase Efl1. Surprisingly, mutations in the P‐site loop of Rpl10, near the catalytic center of the ribosome, inhibit Efl1 function and prevent the release of Tif6, 90Å away. These results suggest an extensive interrogation of the ribosome by Efl1, including assembly of the stalk and the status of the P‐site. Finally, the nuclear export adapter Nmd3 is released, allowing the subunit to enter the pool of active ribosomes and the export adapter to recycle to the nucleus to support another round of export.