Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription
Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription
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DOI：
10.1242/jcs.211094
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发表时间：
2018-04-15
影响因子：
4
通讯作者：
Hozak, Pavel
中科院分区：
文献类型：
--
作者：
Sobol, Margarita;Krausova, Alzbeta;Hozak, Pavel
本文描述了一种新型的核结构——核脂岛（NLI）。它们的直径为 40-100 nm，具有脂质内部，磷脂酰肌醇 4,5-二磷酸 [PtdIns(4,5)P-2] 分子构成其表面的重要部分。大多数 NLI 的外围都有 RNA。与此一致的是，RNA 是其完整性所必需的。 NLI 外围与 Pol II 转录机制相关，包括最大的 Pol II 亚基、转录因子和 NM1（也称为 NMI）。 Ptdlns(4,5)P-2-NM1 相互作用对于 Pol II 转录非常重要，因为 NM1 敲低会降低 Pol II 转录水平，而野生型 NM1 的过表达（但不是 Ptdlns(4,5)P-2 结合位点突变的 NM1）可以挽救转录。重要的是，Pol II 转录依赖于 NLI 完整性，因为 Ptdlns(4,5)P-2 水平的酶促降低会导致 Pol II 转录水平降低。此外，大约一半的新生转录本定位于 NLI，并且转录活性转基因位点优先与 NLI 共定位。我们假设 NLI 作为一个结构平台，促进 Pol II 转录工厂的形成，从而参与能够转录的核结构的形成。
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)P-2] 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 Ptdlns(4,5)P-2-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 Ptdlns(4,5)P-2-binding site] rescues the transcription. Importantly, Pol II transcription is dependent on NLI integrity, because an enzymatic reduction of the Ptdlns(4,5)P-2 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.