Efficient fractionation and analysis of ribosome assembly intermediates in human cells

[EN]Biochemical studies of the human ribosome synthesis pathway have been hindered by technical difficulties in obtaining intact preribosomal complexes from internal regions of the nucleolus. Here we provide a detailed description of an extraction method that enables efficient detection, isolation,...

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Detalles Bibliográficos
Autores: Nieto, Blanca, Gaspar, Sonia G, Sapio, Russell T, Clavaín, Laura, Bustelo, Xosé R., Pestov, Dimitri G, Dosil Castro, Mercedes
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/168975
Acceso en línea:http://hdl.handle.net/10366/168975
Access Level:acceso abierto
Palabra clave:Preribosome
Human nucleolus
pre-rRNA
ribosome maturation
ribosome assembly
preribosome purification
ribosome production
RNA
Ribosomal Proteins
Ribosomes
Humans
Cell Nucleolus
HCT116 Cells
HeLa Cells
RNA Precursors
2415 Biología Molecular
2302 Bioquímica
precursores del ARN
nucleolo celular
humanos
ARN
células HCT116
células HeLa
proteínas ribosómicas
ribosomas
Descripción
Sumario:[EN]Biochemical studies of the human ribosome synthesis pathway have been hindered by technical difficulties in obtaining intact preribosomal complexes from internal regions of the nucleolus. Here we provide a detailed description of an extraction method that enables efficient detection, isolation, and characterization of nucleolar preribosomes containing large pre-rRNA species. The three-step Preribosome Sequential Extraction (PSE) protocol preserves the integrity of early preribosomal complexes and yields preparations amenable to biochemical analyses from low amounts of starting material. We validate this procedure through the detection of specific trans-acting factors and pre-rRNAs in the extracted preribosomes using affinity matrix pull-downs and sedimentation assays. In addition, we describe the application of the PSE method for monitoring cellular levels of ribosome-free 5S RNP complexes as an indicator of ribosome biogenesis stress. Our optimized experimental procedures will facilitate studies of human ribosome biogenesis in normal, mutant and stressed-cell scenarios, including the characterization of candidate ribosome biogenesis factors, preribosome interactors under specific physiological conditions or effects of drugs on ribosome maturation.