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


Church V. A. , Pressman S., Isaji M., Truscott M., Cizmecioglu N. , Buratowski S., ...Daha Fazla

CELL REPORTS, cilt.20, ss.3123-3134, 2017 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 20 Konu: 13
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.celrep.2017.09.010
  • Dergi Adı: CELL REPORTS
  • Sayfa Sayıları: ss.3123-3134

Özet

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.