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

核磷脂酰肌醇 4,5-二磷酸胰岛有助于有效的 RNA 聚合酶 II 依赖性转录

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作者:Margarita Sobol, Alžběta Krausová, Sukriye Yildirim, Ilona Kalasová, Veronika Fáberová, Vladimír Vrkoslav, Vlada Philimonenko, Pavel Marášek, Lukáš Pastorek, Martin Čapek, Zuzana Lubovská, Lívia Uličná, Takuma Tsuji, Miroslav Lísa, Josef Cvačka, Toyoshi Fujimoto, Pavel Hozak

Abstract

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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