Differential regulation of MCM7 and its intronic miRNA cluster miR-106b-25 during megakaryopoiesis induced polyploidy.

Abstract	Megakaryocytes exit from mitotic cell cycle and enter a phase of repeated DNA replication without undergoing cell division, in a process termed as endomitosis of which little is known. We studied the expression of a DNA replication licensing factor mini chromosome maintenance protein 7 (MCM7) and its intronic miR-106b-25 cluster during mitotic and endo-mitotic cycles in megakaryocytic cell lines and in vitro cultured megakaryocytes obtained from human cord blood derived CD34(+) cells. Our results show that contrary to mitotic cell cycle, endomitosis proceeds with an un-coupling of the expression of MCM7 and miR-106b-25. This was attributed to the presence of a transcript variant of MCM7 which undergoes nonsense mediated decay (NMD). Additionally, miR-25 which was up regulated during endomitosis was found to promote megakaryopoiesis by inhibiting the expression of PTEN. Our study thus highlights the importance of a transcript variant of MCM7 destined for NMD in the modulation of megakaryopoiesis.
Authors	Srijan Haldar, Anita Roy, Subrata Banerjee
Journal	RNA biology (RNA Biol) Vol. 11 Issue 9 Pg. 1137-47 ( 2014) ISSN: 1555-8584 [Electronic] United States
PMID	25483046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	MIRN106 microRNA, human MIRN25 microRNA, human MicroRNAs RNA, Messenger PTEN Phosphohydrolase PTEN protein, human MCM7 protein, human Minichromosome Maintenance Complex Component 7
Topics	Blotting, Western Cell Cycle (physiology) Cell Proliferation Cells, Cultured DNA Replication Fetal Blood (cytology, metabolism) Flow Cytometry Gene Expression Regulation Humans Immunoprecipitation Introns (genetics) Megakaryocytes (cytology, metabolism) MicroRNAs (genetics, metabolism) Microscopy, Confocal Minichromosome Maintenance Complex Component 7 (genetics, metabolism) Mitosis (physiology) Nonsense Mediated mRNA Decay (physiology) PTEN Phosphohydrolase (genetics, metabolism) Polyploidy RNA, Messenger (genetics) Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Transcriptional Activation

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