Ribosome Assembly Factors Prevent Premature Translation Initiation by 40S Assembly Intermediates

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Science  11 Aug 2011:
DOI: 10.1126/science.1208245


Ribosome assembly in eukaryotes requires a total of approximately 200 essential assembly factors (AFs), and occurs through ordered events that initiate in the nucleolus and culminate in the cytoplasm. Here, we present the cryo-electron microscopy (cryo-EM) structure of a late cytoplasmic 40S ribosome assembly intermediate from Saccharomyces cerevisiae at 18 Å resolution. The positions of all seven AFs bound to this intermediate were defined using cryo-EM reconstructions of pre-ribosomal complexes lacking individual components. These late-binding AFs are positioned to prevent each step in the translation initiation pathway. Together, they obstruct the binding sites for initiation factors, prevent the opening of the mRNA channel, block 60S subunit joining, and disrupt the decoding site. These redundant mechanisms likely ensure that pre-40S particles do not enter the translation pathway, which would result in their rapid degradation.