Distinct Roles of NANOS1 and NANOS3 in the Cell Cycle and NANOS3-PUM1-FOXM1 Axis to Control G2/M Phase in a Human Primordial Germ Cell Model

Autor:	Kamila Kusz-Zamelczyk, Krystyna Kwiatkowska, Damian Mikołaj Janecki, Żaneta Lemańska, Jadwiga Jaruzelska, Marcin Sajek, Erkut Ilaslan, Maciej Smialek, Matisa Alla
Rok vydání:	2022
Předmět:	Male Mammals Cell Cycle Forkhead Box Protein M1 Organic Chemistry RNA-Binding Proteins General Medicine Catalysis Computer Science Applications Inorganic Chemistry Germ Cells Infertility Animals Humans RNA Messenger Physical and Theoretical Chemistry Molecular Biology NANOS1 NANOS3 PUM1 FOXM1 human primordial germ cells cell cycle germ cell cancer Cell Division Spectroscopy Transcription Factors
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 12; Pages: 6592
ISSN:	1422-0067
DOI:	10.3390/ijms23126592
Popis:	Nanos RNA-binding proteins are critical factors of germline development throughout the animal kingdom and their dysfunction causes infertility. During evolution, mammalian Nanos paralogues adopted divergent roles in germ cell biology. However, the molecular basis behind this divergence, such as their target mRNAs, remains poorly understood. Our RNA-sequencing analysis in a human primordial germ cell model-TCam-2 cell line revealed distinct pools of genes involved in the cell cycle process downregulated upon NANOS1 and NANOS3 overexpression. We show that NANOS1 and NANOS3 proteins influence different stages of the cell cycle. Namely, NANOS1 is involved in the G1/S and NANOS3 in the G2/M phase transition. Many of their cell cycle targets are known infertility and cancer-germ cell genes. Moreover, NANOS3 in complex with RNA-binding protein PUM1 causes 3′UTR-mediated repression of FOXM1 mRNA encoding a transcription factor crucial for G2/M phase transition. Interestingly, while NANOS3 and PUM1 act as post-transcriptional repressors of FOXM1, FOXM1 potentially acts as a transcriptional activator of NANOS3, PUM1, and itself. Finally, by utilizing publicly available RNA-sequencing datasets, we show that the balance between FOXM1-NANOS3 and FOXM1-PUM1 expression levels is disrupted in testis cancer, suggesting a potential role in this disease.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf4ee270a15e09c7b9e9886b1f053ee2 https://doi.org/10.3390/ijms23126592 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.