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Highly conserved ribosome biogenesis pathways between human and yeast revealed by the MDN1-NLE1 interaction and NLE1 containing pre-60S subunits

The assembly of ribosomal subunits, primarily occurring in the nucleolar and nuclear compartments, is a highly complex process crucial for cellular function. This study reveals the conservation of ribosome biogenesis between yeast and humans, illustrated by the structural similarities of ribosomal s...

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Main Authors: Fiorentino, Federica (Author) , Thoms, Matthias (Author) , Wild, Klemens (Author) , Denk, Timo (Author) , Cheng, Jingdong (Author) , Zeman, Jakub (Author) , Sinning, Irmgard (Author) , Hurt, Ed (Author) , Beckmann, Roland (Author)
Format: Article (Journal)
Language:English
Published: 24 April 2025
In: Nucleic acids research
Year: 2025, Volume: 53, Issue: 7, Pages: 1-14
ISSN:1362-4962
DOI:10.1093/nar/gkaf255
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/nar/gkaf255
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Author Notes:Federica Fiorentino, Matthias Thoms, Klemens Wild, Timo Denk, Jingdong Cheng, Jakub Zeman, Irmgard Sinning, Ed Hurt, Roland Beckmann
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Summary:The assembly of ribosomal subunits, primarily occurring in the nucleolar and nuclear compartments, is a highly complex process crucial for cellular function. This study reveals the conservation of ribosome biogenesis between yeast and humans, illustrated by the structural similarities of ribosomal subunit intermediates. By using X-ray crystallography and cryo-EM, the interaction between the human AAA+ ATPase MDN1 and the 60S assembly factor NLE1 is compared with the yeast homologs Rea1 and Rsa4. The MDN1-MIDAS and NLE1-Ubl complex structure at 2.3 Å resolution mirrors the highly conserved interaction patterns observed in yeast. Moreover, human pre-60S intermediates bound to the dominant negative NLE1-E85A mutant revealed at 2.8 Å resolution an architecture that largely matched the equivalent yeast structures. Conformation of rRNA, assembly factors and their interaction networks are highly conserved. Additionally, novel human pre-60S intermediates with a non-rotated 5S RNP and processed ITS2/foot structure but incomplete intersubunit surface were identified to be similar to counterparts observed in yeast. These findings confirm that the MDN1-NLE1-driven transition phase of the 60S assembly is essentially identical, supporting the idea that ribosome biogenesis is a highly conserved process across eukaryotic cells, employing an evolutionary preservation of ribosomal assembly mechanisms.
Item Description:Gesehen am 30.09.2025
Physical Description:Online Resource
ISSN:1362-4962
DOI:10.1093/nar/gkaf255

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