CONTEXT

microRNAs play critical roles in the control of gene expression at the post-transcriptional level. These tiny regulatory RNAs (~19-23 nt in length) base-pair preferentially with the 3’ un-translated region of mRNAs and trigger either degradation or translation inhibition of the targeted mRNAs. Through their ability to interact with numerous mRNAs, microRNAs are involved in diverse developmental and physiological events. Over the past few years, a myriad of papers has described aberrant microRNA expression profiles in pathological situations, notably in neurological disorders, cardiovascular disease,viral infections and cancers.  microRNAs represent therefore novel and promising “therapeutic targets” or “therapeutic agents” and there are considerable efforts worldwide in manipulating their expression in vivo, with as an ultimate goal the rescue of microRNA-mediated gene regulation in those pathological contexts.

In animals, miRNA biogenesis initiates in the nucleus where long Pol-II, primary transcripts (pri-miRNA) are first processed into irregular, 70 nt hairpin-shaped RNA intermediate (pre-miRNAs) by the Drosha-DGCR8 (Microprocessor) complex. Recent emerging data support the view that the activity and specificity of Microprocessor is subject to important post-transcriptional regulation in a widespread manner during early development or in some cancers. Therefore, any drugs modifying Microprocessor expression/stability, RNA-binding activity, interacting protein partner, intra-nuclear distribution will also alter significantly the cellular content of microRNAs.