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

Victoria A. Church, Sigal Pressman, Mamiko Isaji, Mary Truscott, Nihal Terzi Cizmecioglu, Stephen Buratowski, Maxim V. Frolov, Richard W. Carthew*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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. Nuclear processing of microRNAs is a major determinant of cellular abundance of these RNAs. Church et al. find that the DGCR8 subunit of Microprocessor binds to RNA polymerase II. This couples microRNA processing to transcription. If microRNAs lack a sequence motif, co-transcriptional processing plays a more important role in determining abundance.

Original languageEnglish (US)
Pages (from-to)3123-3134
Number of pages12
JournalCell reports
Volume20
Issue number13
DOIs
Publication statusPublished - Sep 26 2017

    Fingerprint

Keywords

  • DGCR8
  • Drosophila
  • RNA polymerase II
  • microRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this