Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs

Alexander C. Partin, Tri D. Ngo, Emily Herrell, Byung Cheon Jeong, Gary Hon, Yunsun Nam

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

MicroRNAs regulate the expression of many proteins and require specific maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by Microprocessor, a complex containing the RNase Drosha and its partner protein, DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in pri-miR processing is unknown. Here we show that heme is critical for Microprocessor to process pri-miRs with high fidelity. Furthermore, the degree of inherent heme dependence varies for different pri-miRs. Heme-dependent pri-miRs fail to properly recruit Drosha, but heme-bound DGCR8 can correct erroneous binding events. Rather than changing the oligomerization state, heme induces a conformational change in DGCR8. Finally, we demonstrate that heme activates DGCR8 to recognize pri-miRs by specifically binding the terminal loop near the 3′ single-stranded segment.

Original languageEnglish (US)
Article number1737
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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