RNA helicase Drs1 gates 25S rRNA domain III incorporation during early nucleolar pre-60S maturation
Year: 2026
Type: preprint
Abstract: ABSTRACT Assembly of eukaryotic large ribosomal subunits (LSU) requires coordinated structural and compositional transitions within pre-60S particles, yet the underlying mechanisms remain poorly understood. Here, we show that the DEAD-box helicase Drs1 promotes early maturation across distinct regions of the pre-60S particle. Loss of Drs1 function causes accumulation of co-transcriptional intermediates retaining SSU processome components, indicating that Drs1 promotes timely separation of nascent LSU precursors from the small-subunit assembly pathway. Cryo-EM analyses reveal both a redistribution toward early nucleolar maturation states upon loss of Drs1, including Nsa1-deficient intermediates, and a confinement of Drs1-associated particles to states preceding stable incorporation of 25S rRNA domain III. Drs1 directly engages Erb1 through its unstructured N-terminal extension, promoting stable assembly of the Nop7-Erb1-Ytm1 module associated with domain III maturation. CRAC analysis localizes Drs1 to spatially clustered sites spanning the 5.8S and 25S rRNAs, encompassing domains I–IV. Together, these findings support a model in which Drs1 couples stabilization of assembly-factors with pre-rRNA remodeling across the pre-60S particle, thereby driving ordered early LSU maturation and the timed integration of domain III.
Institutions: Ludwig-Maximilians-Universität München, University of Graz, Centre National de la Recherche Scientifique, Université Toulouse III - Paul Sabatier, Université de Toulouse, Unité de biologie Moléculaire, Cellulaire et du Développement, Centre de Biologie Intégrative de Toulouse, Heidelberg University, Max Planck Institute of Biochemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1633438099, Mechanisms of RNA helicases in ribosome assembly, G2450077225, G4964816082, The dual life of RNA Polymerase I and snoRNP disordered KKE/D domains: from rRNA modification to nucleolar compaction, G6407871267, Ribosome biogenesis: The yin and yang of protein homeostasis, Functions of the AAA-ATPase Rix7 in pre-60S assembly, Initial events of large ribosomal subunit formation in eukaryotes, G715650138, G8590477180
OpenAlex ID: W7212195461