Download MendeleyHighly conserved ribosome biogenesis pathways between human and yeast revealed by the MDN1-NLE1 interaction and NLE1 containing pre-60S subunits.
Fiorentino, F., Thoms, M., Wild, K., Denk, T., Cheng, J., Zeman, J., Sinning, I., Hurt, E., Beckmann, R.(2025) Nucleic Acids Res 53
- PubMed: 40207627
- DOI: https://doi.org/10.1093/nar/gkaf255
- Primary Citation of Related Structures:
8QL1, 8RL2, 9QIW - PubMed Abstract:
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 ? 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 ? 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.
Organizational Affiliation:
Biochemistry Center (BZH), University of Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
