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

• Published in: Journal of cell science Vol. 131; no. 8; p. jcs211094
• Main Authors: Sobol, Margarita, Krausová, Alžběta, Yildirim, Sukriye, Kalasová, Ilona, Fáberová, Veronika, Vrkoslav, Vladimír, Philimonenko, Vlada, Marášek, Pavel, Pastorek, Lukáš, Čapek, Martin, Lubovská, Zuzana, Uličná, Lívia, Tsuji, Takuma, Lísa, Miroslav, Cvačka, Josef, Fujimoto, Toyoshi, Hozak, Pavel
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15.04.2018
• Subjects: Architecture; Binding sites; DNA-directed RNA polymerase; Factories; Industrial plants; Integrity; Molecular chains; Nuclear structure; Phosphatidylinositol 4,5-diphosphate; Ribonucleic acid; RNA; RNA polymerase II; Transcription factors; PtdIns(4,5)P2; Nucleus; Chromatin; Phosphoinositides; RNA polymerase II; DNA transcription
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.211094

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 ] 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)P -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)P -binding site] rescues the transcription. Importantly, Pol II transcription is dependent on NLI integrity, because an enzymatic reduction of the PtdIns(4,5)P 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.