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Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription

M. Sobol, A. Krausová, S. Yildirim, I. Kalasová, V. Fáberová, V. Vrkoslav, V. Philimonenko, P. Marášek, L. Pastorek, M. Čapek, Z. Lubovská, L. Uličná, T. Tsuji, M. Lísa, J. Cvačka, T. Fujimoto, P. Hozak,

. 2018 ; 131 (8) : . [pub] 20180413

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19045533

This paper describes a novel type of nuclear structure - nuclear lipid islets (NLIs). They are of 40-100 nm with a lipidic interior, and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] molecules comprise a significant part of their surface. Most of NLIs have RNA at the periphery. Consistent with that, RNA is required for their integrity. The NLI periphery is associated with Pol II transcription machinery, including the largest Pol II subunit, transcription factors and NM1 (also known as NMI). The PtdIns(4,5)P2-NM1 interaction is important for Pol II transcription, since NM1 knockdown reduces the Pol II transcription level, and the overexpression of wild-type NM1 [but not NM1 mutated in the PtdIns(4,5)P2-binding site] rescues the transcription. Importantly, Pol II transcription is dependent on NLI integrity, because an enzymatic reduction of the PtdIns(4,5)P2 level results in a decrease of the Pol II transcription level. Furthermore, about half of nascent transcripts localise to NLIs, and transcriptionally active transgene loci preferentially colocalise with NLIs. We hypothesize that NLIs serve as a structural platform that facilitates the formation of Pol II transcription factories, thus participating in the formation of nuclear architecture competent for transcription.

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$a Sobol, Margarita $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription / $c M. Sobol, A. Krausová, S. Yildirim, I. Kalasová, V. Fáberová, V. Vrkoslav, V. Philimonenko, P. Marášek, L. Pastorek, M. Čapek, Z. Lubovská, L. Uličná, T. Tsuji, M. Lísa, J. Cvačka, T. Fujimoto, P. Hozak,
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$a This paper describes a novel type of nuclear structure - nuclear lipid islets (NLIs). They are of 40-100 nm with a lipidic interior, and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] molecules comprise a significant part of their surface. Most of NLIs have RNA at the periphery. Consistent with that, RNA is required for their integrity. The NLI periphery is associated with Pol II transcription machinery, including the largest Pol II subunit, transcription factors and NM1 (also known as NMI). The PtdIns(4,5)P2-NM1 interaction is important for Pol II transcription, since NM1 knockdown reduces the Pol II transcription level, and the overexpression of wild-type NM1 [but not NM1 mutated in the PtdIns(4,5)P2-binding site] rescues the transcription. Importantly, Pol II transcription is dependent on NLI integrity, because an enzymatic reduction of the PtdIns(4,5)P2 level results in a decrease of the Pol II transcription level. Furthermore, about half of nascent transcripts localise to NLIs, and transcriptionally active transgene loci preferentially colocalise with NLIs. We hypothesize that NLIs serve as a structural platform that facilitates the formation of Pol II transcription factories, thus participating in the formation of nuclear architecture competent for transcription.
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$a fosfatidylinositol-4,5-difosfát $x metabolismus $7 D019269
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$a Krausová, Alžběta $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Yildirim, Sukriye $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Kalasová, Ilona $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Fáberová, Veronika $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Vrkoslav, Vladimír $u Institute of Organic Chemistry and Biochemistry, CAS, v.v.i., Research Service Group of Mass Spectrometry, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
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$a Philimonenko, Vlada $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic. Institute of Molecular Genetics, CAS, v.v.i., Electron Microscopy Core Facility, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Marášek, Pavel $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Pastorek, Lukáš $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic. Institute of Molecular Genetics, CAS, v.v.i., Electron Microscopy Core Facility, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Čapek, Martin $u Institute of Molecular Genetics, CAS, v.v.i., Light Microscopy Core Facility, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Lubovská, Zuzana $u Institute of Molecular Genetics, CAS, v.v.i., Electron Microscopy Core Facility, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Uličná, Lívia $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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$a Tsuji, Takuma $u Nagoya University Graduate School of Medicine, Department of Molecular Cell Biology, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
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$a Lísa, Miroslav $u University of Pardubice, Faculty of Chemical Technology, Department of Analytical Chemistry, Studentská 573, 532 10, Pardubice, Czech Republic.
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$a Cvačka, Josef $u Institute of Organic Chemistry and Biochemistry, CAS, v.v.i., Research Service Group of Mass Spectrometry, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
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$a Fujimoto, Toyoshi $u Nagoya University Graduate School of Medicine, Department of Molecular Cell Biology, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
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$a Hozak, Pavel $u Institute of Molecular Genetics, CAS, v.v.i., Department of Biology of the Cell Nucleus, Vídeňská 1083, 142 20, Prague 4, Czech Republic hozak@img.cas.cz. Institute of Molecular Genetics, CAS, v.v.i., Division BIOCEV, Laboratory of Epigenetics of the Cell Nucleus, Průmyslová 595, 252 50, Vestec, Czech Republic. Institute of Molecular Genetics, CAS, v.v.i., Microscopy Centre, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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