Cargando…

Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division

Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles a...

Descripción completa

Detalles Bibliográficos
Autores principales: Grob, Alice, Colleran, Christine, McStay, Brian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923965/
https://www.ncbi.nlm.nih.gov/pubmed/24449107
http://dx.doi.org/10.1101/gad.234591.113
_version_ 1782303680392855552
author Grob, Alice
Colleran, Christine
McStay, Brian
author_facet Grob, Alice
Colleran, Christine
McStay, Brian
author_sort Grob, Alice
collection PubMed
description Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly.
format Online
Article
Text
id pubmed-3923965
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-39239652014-02-21 Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division Grob, Alice Colleran, Christine McStay, Brian Genes Dev Research Paper Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly. Cold Spring Harbor Laboratory Press 2014-02-01 /pmc/articles/PMC3923965/ /pubmed/24449107 http://dx.doi.org/10.1101/gad.234591.113 Text en © 2014 Grob et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Paper
Grob, Alice
Colleran, Christine
McStay, Brian
Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title_full Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title_fullStr Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title_full_unstemmed Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title_short Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
title_sort construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923965/
https://www.ncbi.nlm.nih.gov/pubmed/24449107
http://dx.doi.org/10.1101/gad.234591.113
work_keys_str_mv AT grobalice constructionofsyntheticnucleoliinhumancellsrevealshowamajorfunctionalnucleardomainisformedandpropagatedthroughcelldivision
AT colleranchristine constructionofsyntheticnucleoliinhumancellsrevealshowamajorfunctionalnucleardomainisformedandpropagatedthroughcelldivision
AT mcstaybrian constructionofsyntheticnucleoliinhumancellsrevealshowamajorfunctionalnucleardomainisformedandpropagatedthroughcelldivision