Helicase-mediated mechanism of SSU processome maturation and disassembly

Eukaryotic ribosomal small subunit (SSU) assembly requires the SSU processome, a nucleolar precursor containing the RNA chaperone U3 snoRNA. The underlying molecular mechanisms of SSU processome maturation, remodeling, disassembly, RNA quality control, and the transitions between states remain elusive due to a paucity of intermediates ^1-3 . Here we report 16 native SSU processome structures alongside genetic data, revealing how two helicases, the Mtr4-exosome and Dhr1, are controlled for accurate and unidirectional ribosome biogenesis. Our data show how irreversible pre-ribosomal RNA degradation by the redundantly tethered RNA exosome couples the transformation of the SSU processome into a pre-40 S particle during which Utp14 can probe evolving surfaces, ultimately positioning and activating Dhr1 to unwind the U3 snoRNA and initiate nucleolar pre-40 S release. This study highlights a paradigm for large dynamic RNA-protein complexes where irreversible RNA degradation drives compositional changes and communicates these changes to govern enzyme activity while maintaining overall quality control.