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Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs.

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.

SUBMITTER: Partin AC

PROVIDER: S-EPMC5700927 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs.

Partin Alexander C AC Ngo Tri D TD Herrell Emily E Jeong Byung-Cheon BC Hon Gary G Nam Yunsun Y

Nature communications 20171123 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 ...[more]

PMID: 29170488

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