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Microprocessor Recruitment to RNA Polymerase II is Required for Differential Expression of MicroRNAs

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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.

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  • 01/29/2019
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