Dynamic architecture of the Rixosome reveals mechanism of activation and ITS2 processing
- 1Eye & ENT Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Abstract
Eukaryotic ribosome assembly requires the coordinated processing and extensive remodeling of pre-rRNAs. During late nuclear maturation of the 60S subunit, sequential removal of the internal transcribed spacer 2 (ITS2) is initiated by endonucleolytic cleavage at site C2 by the conserved Las1 nuclease. Las1 acts together with the kinase Grc3 and the Rix1 complex to form the Rixosome, which also functions in transcriptional regulation. However, the assembly of the Rixosome, its recruitment to pre-ribosomes, and its activation for ITS2 cleavage remain unclear. Here, we present cryo-EM structures of the human LAS1 complex, two structures of the isolated Rixosome and nine transition states of Rix1-bound pre-60S particles from Schizosaccharomyces pombe. These structures reveal a dynamic Rixosome architecture in which the heterotetrameric Las1 complex engages one or two copies of the Rix1 complex. Rix1 binding is highly flexible in the human Rixosome but rigid in the yeast complex. The isolated yeast Rixosome remains inactive, but binding to the pre-60S particle triggers a structural rearrangement that allows for substrate engagement and activation of the nuclease. Together, our results define the dynamic architecture of the Rixosome and provide a structural framework for ITS2 processing during nuclear maturation of the eukaryotic 60S ribosomal subunit.
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BibTeX
@misc{thoms2026dynamic,
title = {{Dynamic architecture of the Rixosome reveals mechanism of activation and ITS2 processing}},
author = {M. Thoms and J. Zhu and X. Hong and T. Denk and J. Stritzel and S. Niu and O. Berninghausen and Y. Li and J. Liu and R. Beckmann and J. Cheng},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750072},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750072v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Dynamic architecture of the Rixosome reveals mechanism of activation and ITS2 processing
AU - M. Thoms
AU - J. Zhu
AU - X. Hong
AU - T. Denk
AU - J. Stritzel
AU - S. Niu
AU - O. Berninghausen
AU - Y. Li
AU - J. Liu
AU - R. Beckmann
AU - J. Cheng
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750072
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750072v1
AB - Eukaryotic ribosome assembly requires the coordinated processing and extensive remodeling of pre-rRNAs. During late nuclear maturation of the 60S subunit, sequential removal of the internal transcribed spacer 2 (ITS2) is initiated by endonucleolytic cleavage at site C2 by the conserved Las1 nuclease. Las1 acts together with the kinase Grc3 and the Rix1 complex to form the Rixosome, which also functions in transcriptional regulation. However, the assembly of the Rixosome, its recruitment to pre-ribosomes, and its activation for ITS2 cleavage remain unclear. Here, we present cryo-EM structures of the human LAS1 complex, two structures of the isolated Rixosome and nine transition states of Rix1-bound pre-60S particles from Schizosaccharomyces pombe. These structures reveal a dynamic Rixosome architecture in which the heterotetrameric Las1 complex engages one or two copies of the Rix1 complex. Rix1 binding is highly flexible in the human Rixosome but rigid in the yeast complex. The isolated yeast Rixosome remains inactive, but binding to the pre-60S particle triggers a structural rearrangement that allows for substrate engagement and activation of the nuclease. Together, our results define the dynamic architecture of the Rixosome and provide a structural framework for ITS2 processing during nuclear maturation of the eukaryotic 60S ribosomal subunit.
ER -