Regulation of microRNAs and analysis of the splicing inhibitor Spliceostatin A

The advent of deep sequencing has revealed marked differences in microRNA (miRNA) expression profiles between cell types. We focus on how miRNAs are regulated in embryonic stem cells (ESCs) and their differentiated neural progenitor stem cells (NPSCs). We discovered that 60% of miRNAs are regulated b y transcription. The remaining 40% of miRNAs were transcribed but not processed in ESCs. Furthermore, systematic analysis of miRNAs on chromosome 1 and 2 helped to validate our results. We show that 43% of these miRNAs, which are highly expressed in differentiated cell types but poorly expressed in ESCs, were transcribed but not processed in ESCs. Therefore we infer that post- transcr iptional regulation of miRNAs is prevalent in ESCs and could potentially be a characteristic of this cell type. Post-transcriptional regulation of miRNAs is also evident in miRNA clusters. Clusters of miRNAs are transcribed together however individual mature miRNA expression often differs between tissues and even within the same tissue type. Following investigation into post-transcriptional regulation, we discovered extensive alternative polyadenylation in three different miRNA clusters. We suggest that alternative polyadenylation has the potential to influence regulation of individual miRNAs within a cluster contributing to their differential expression levels.Open Acces