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bioRxiv · 10.1101/2025.09.29.679232

Helicase-mediated mechanism of SSU processome maturation and disassembly

Klinge, S.·Buzovetsky, O.
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Abstract

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 intermediates1-3. 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-40S particle during which Utp14 can probe evolving surfaces, ultimately positioning and activating Dhr1 to unwind the U3 snoRNA and initiate nucleolar pre-40S 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.

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Klinge, S., Buzovetsky, O.. 2025-09-29. Helicase-mediated mechanism of SSU processome maturation and disassembly. https://doi.org/10.1101/2025.09.29.679232

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