Abstract
Naïve pluripotent embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent distinctive developmental stages, mimicking the pre- and the post-implantation events during the embryo development, respectively. The complex molecular mechanisms governing the transition from ESCs into EpiSCs are orchestrated by fluctuating levels of pluripotency transcription factors (Nanog, Oct4, etc.) and wide-ranging remodeling of the epigenetic landscape. Recent studies highlighted the pivotal role of microRNAs (miRNAs) in balancing the switch from self-renewal to differentiation of ESCs. Of note, evidence deriving from miRNA-based reprogramming strategies underscores the role of the non-coding RNAs in the induction and maintenance of the stemness properties. In this review, we revised recent studies concerning the functions mediated by miRNAs in ESCs, with the aim of giving a comprehensive view of the highly dynamic miRNA-mediated tuning, essential to guarantee cell cycle progression, pluripotency maintenance and the proper commitment of ESCs.
Highlights
MicroRNAs are small non-coding RNA molecules, approximately 23 nucleotides in length, able to regulate the expression of a large set of genes
The results reviewed above demonstrate that the regulatory mechanisms underlying the state of embryonic stem cells (ESCs) are based on dynamic regulation of microRNAs
Kanellopoulou and colleagues demonstrated that the Hox genes, which are associated with ESC differentiation, are regulated at transcriptional level by mir-290 cluster
Summary
MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 23 nucleotides (nt) in length, able to regulate the expression of a large set of genes. The first step of the pri-miRNA processing occurs in the nucleus and involves a stem–loop cropping, mediated by the microprocessor complex containing RNase III-type enzyme DROSHA and the RNA-binding protein DGCR8 [6,7,8]. This precursor, called pre-miRNA (approximately 65 nt in length), is exported in the cytoplasm by EXPORTIN 5 and cleaved near the terminal loop by the RNAse III type endonuclease DICER, generating a small miRNA duplex intermediate (approximately 22 nt in length) [9,10]. MicroRNAs contribute to stem cell maintenance and fate decisions as well as the establishment of pluripotency
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