New connections between microRNAs transcription and processing

To date microRNA precursors have been described as long capped and polyadenilated transcripts, mostly transcribed by RNA polymerase II. The 21 nucleotides miRNAs are generated by a nucleo-cytoplasmic processing cascade. The nuclear processing machinery is composed of two key factors, the RNAse III Drosha and its partner DGCR8. The early steps of the pri-miRNA procesing have been described in vitro as separate and post transcriptional events occurring on discrete precursors, while using the in vivo ChIP assay, we demonstrate the co-transcriptional recruitment of Drosha protein to miRNA genomic loci. We show that this interaction requires structural determinants in the RNA substrate. Moreover, a canonical RNA-pol II cleavage and polyadenilation site downstream to miRNAs interferes with Drosha processing, suggesting a competition between these two events on the same transcriptional unit. Since Drosha association on pri-miRNA occurs co-transcriptionally and its processing defines pre-miRNA 3’-end, we tested the effects of Drosha activity on transcription. We find that a co-transcriptional cleavage leads to negative effects on elongation suggesting a possible interplay between transcription and processing in vivo. Taken together our data suggest a “miRNA-factory” model that ensures a correct and efficient production of the physiological miRNA precursors.