Microprocessor Recruitment to RNA Polymerase II is Required for Differential Expression of MicroRNAsPublic Deposited
The cellular abundance of mature microRNAs (miRNAs) is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs) into pre-miRNA intermediates. The Microprocessor complex, composed of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor's differential processing of various pri-miRNAs. Here, I show that Drosophila DGCR8 (Pasha) directly associates with the C-terminal domain of the RNA polymerase II elongation complex when it is phosphorylated by the Cdk9 kinase (pTEFb). When association is blocked by loss of Cdk9 activity, a global change in pri-miRNA processing is detected. Processing of pri- miRNAs with a canonical sequence motif in their apical junction domain increases, while processing of pri-miRNAs lacking this canonical sequence decreases. Therefore, phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-canonical pri-miRNAs that would otherwise be poorly processed. In contrast, canonical pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association.