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

作者：Haldar Srijan; Roy Anita; Banerjee Subrata^*

来源：RNA Biology, 2014, 11(9): 1137-1147.

DOI：10.4161/rna.36136

• megakaryopoiesis
• polyploidy
• MCM7
• miRNA
• Nonsense mediated decay
• PTEN
• qRT-PCR
• quantitative real time polymerase chain reaction
• FACS
• Fluorescence Activated Cell Sorting
• HPRT
• Hypoxanthine PhosphoRibosyl Transferase
• APC
• Allophycocyanin
• PE
• R-phycoerythrin
• RIPA
• Radio immuno precipitation Assay

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.

• 出版日期2014-9