Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
19
06
2021
accepted:
26
03
2023
medline:
23
8
2023
pubmed:
9
6
2023
entrez:
8
6
2023
Statut:
ppublish
Résumé
The 5S ribonucleoprotein (RNP) is assembled from its three components (5S rRNA, Rpl5/uL18 and Rpl11/uL5) before being incorporated into the pre-60S subunit. However, when ribosome synthesis is disturbed, a free 5S RNP can enter the MDM2-p53 pathway to regulate cell cycle and apoptotic signaling. Here we reconstitute and determine the cryo-electron microscopy structure of the conserved hexameric 5S RNP with fungal or human factors. This reveals how the nascent 5S rRNA associates with the initial nuclear import complex Syo1-uL18-uL5 and, upon further recruitment of the nucleolar factors Rpf2 and Rrs1, develops into the 5S RNP precursor that can assemble into the pre-ribosome. In addition, we elucidate the structure of another 5S RNP intermediate, carrying the human ubiquitin ligase Mdm2, which unravels how this enzyme can be sequestered from its target substrate p53. Our data provide molecular insight into how the 5S RNP can mediate between ribosome biogenesis and cell proliferation.
Identifiants
pubmed: 37291423
doi: 10.1038/s41594-023-01006-7
pii: 10.1038/s41594-023-01006-7
pmc: PMC10442235
doi:
Substances chimiques
RNA, Ribosomal, 5S
0
Tumor Suppressor Protein p53
0
Ribosomal Proteins
0
Ribonucleoproteins
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1119-1131Informations de copyright
© 2023. The Author(s).
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