miRNA 146b mediates the regulation of nucleolar size and activity in polyploid megakaryocytes

Abstract

Background InformationMegakaryocytes (MKs) follow a unique cell cycle duplication process, called endomitosis, resulting in polyploidisation of cells. It is hypothesised that polyploidy, as well as an increment in cytoplasm volume, allow more efficient platelets generation from MKs. Although polyploidy leads to an increase in the DNA amount, which impacts gene expression, little is known about ribosomal biogenesis in these polylobulated polyploid cells.ResultsThe nucleolus acts as a hub for ribosomal biogenesis, which in turn governs the protein synthesis rate of the cells. We therefore estimated the size and activity of the nucleolus in polyploid cells during megakaryopoiesis in vitro. Polyploid megakaryocytic cell lines and in vitro cultured MKs, which were obtained from human cord blood‐derived CD 34+ cells, revealed that miRNA 146b regulated the activity of nucleolar and coiled‐body phosphoprotein 1, which plays an integral role in determining nucleolar size and activity. Additionally, miRNA‐146b was up‐regulated during endomitosis and was found to promote megakaryopoiesis.ConclusionWe propose that miRNA 146b regulates not only nucleolar size and activity, but also megakaryopoiesis.SignificanceThis study highlights the importance of nucleolar activity and miRNA in the progression of megakaryopoiesis and thrombopoiesis.

Comparative transcriptome and proteome reveal synergistic functions of differentially expressed genes and proteins implicated in an over‐dominant silkworm heterosis of increased silk yield

“…Knockdown of fibrillarin could severely decrease the methylation of pre‐rRNA and significantly inhibit translation initiation for IRES (internal ribosome entry site)‐dependent ones, such as for various viruses, but not Cap‐dependent ones, such as for silk proteins. NOLC1 and fibrillarin are down‐regulated during the human megakaryopoiesis accompanied with reduced rRNA and protein synthesis and are decreased in higher ploidy cells compared to lower ploidy cells (Chattopadhyaya & Banerjee, 2021), indicating their down‐regulation promotes endomitosis. Interestingly, NOLC1 is greatly down‐regulated in domesticated silkworms as compared to wild silkworms, indicating it is negatively correlated with silk yield (J. Y. Li et al, 2017).…”