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

2017-09-26
Church, Victoria A.
Pressman, Sigal
Isaji, Mamiko
Truscott, Mary
Terzi Çizmecioğlu, Nihal
Buratowski, Stephen
Frolov, Maxim V.
Carthew, Richard W.
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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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 of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor's differential processing of various pri-miRNAs. Here, we 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 UGU sequence motif in their apical junction domain increases, while processing of pri-miRNAs lacking this motif decreases. Therefore, phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-UGU pri-miRNAs that would otherwise be poorly processed. In contrast, UGU-positive pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association.
Kinase, Recognition, Drosophila, Transcription, In-vivo; p-tefb, Mammalian-cells, Drosha-dgcr8 complex, mirna biogenesis, Heat-shock genes
https://hdl.handle.net/11511/42244
Department of Biology, Article

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Citation Formats
V. A. Church et al., “Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs,” CELL REPORTS, pp. 3123–3134, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/42244.
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