Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs

Alexander C. Partin, Tri D. Ngo, Emily Herrell, Byung-Cheon Jeong, Gary Hon and Yunsun Nam ()
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Alexander C. Partin: University of Texas Southwestern Medical Center
Tri D. Ngo: University of Texas Southwestern Medical Center
Emily Herrell: University of Texas Southwestern Medical Center
Byung-Cheon Jeong: University of Texas Southwestern Medical Center
Gary Hon: University of Texas Southwestern Medical Center
Yunsun Nam: University of Texas Southwestern Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01713-y

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