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A Systems-Level Study Reveals Regulators of Membrane-less Organelles in Human Cells.
Berchtold, Doris; Battich, Nico; Pelkmans, Lucas.
Afiliación
  • Berchtold D; Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
  • Battich N; Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
  • Pelkmans L; Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland. Electronic address: lucas.pelkmans@imls.uzh.ch.
Mol Cell ; 72(6): 1035-1049.e5, 2018 12 20.
Article en En | MEDLINE | ID: mdl-30503769
ABSTRACT
Membrane-less organelles (MLOs) are liquid-like subcellular compartments that form through phase separation of proteins and RNA. While their biophysical properties are increasingly understood, their regulation and the consequences of perturbed MLO states for cell physiology are less clear. To study the regulatory networks, we targeted 1,354 human genes and screened for morphological changes of nucleoli, Cajal bodies, splicing speckles, PML nuclear bodies (PML-NBs), cytoplasmic processing bodies, and stress granules. By multivariate analysis of MLO features we identified hundreds of genes that control MLO homeostasis. We discovered regulatory crosstalk between MLOs, and mapped hierarchical interactions between aberrant MLO states and cellular properties. We provide evidence that perturbation of pre-mRNA splicing results in stress granule formation and reveal that PML-NB abundance influences DNA replication rates and that PML-NBs are in turn controlled by HIP kinases. Together, our comprehensive dataset is an unprecedented resource for deciphering the regulation and biological functions of MLOs.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Estrés Fisiológico / Orgánulos / Biología de Sistemas / Transcriptoma Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Estrés Fisiológico / Orgánulos / Biología de Sistemas / Transcriptoma Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Suiza