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TitleStructure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 8, Page 1119-1131, Year 2023
Publish dateJun 8, 2023
AuthorsNestor Miguel Castillo Duque de Estrada / Matthias Thoms / Dirk Flemming / Henrik M Hammaren / Robert Buschauer / Michael Ameismeier / Jochen Baßler / Martin Beck / Roland Beckmann / Ed Hurt /
PubMed AbstractThe 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 ...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.
External linksNat Struct Mol Biol / PubMed:37291423 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 4.1 Å
Structure data

13134

7ozs

EMDB-13134, PDB-7ozs:
Structure of the hexameric 5S RNP from C. thermophilum
Method: EM (single particle) / Resolution: 3.5 Å

16036

8bgu

EMDB-16036, PDB-8bgu:
human MDM2-5S RNP
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-16037: hexameric ct-sc 5S RNP monomer
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-16038: hexameric ct-sc 5S RNP dimer
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-16040: pre-60S with human 5S RNP
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
  • thermochaetoides thermophila dsm 1495 (fungus)
  • homo sapiens (human)
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRNA BINDING PROTEIN / 5S RNP / Ribosome biogenesis / Symportin 1 / Rpf2-Rrs1 / Mdm2

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