biostudies-literature00550Partin ACNIGMS NIH HHS1737https://www.ebi.ac.uk/biostudies/studies/S-EPMC5700927biostudies-literatureUnknown8(1)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.Nature communicationsHeme enables proper positioning of Drosha and DGCR8 on primary microRNAs.PMC5700927R01 GM122960Ngo TDHon GJeong BCHerrell ENam YPartin AC55falseHeme enables proper positioning of Drosha and DGCR8 on primary microRNAs.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.2017-01-01T00:00:00Z2017 Nov2024-11-12T16:59:02.294Z2019-03-26T23:56:30ZS-EPMC57009272917048810.1038/s41467-017-01713-y