title: Heme is involved in microRNA processing.
abstract: MicroRNAs (miRNAs) regulate the expression of a large number of protein-coding genes. Their primary transcripts (pri-miRNAs) have to undergo multiple processing steps to reach the functional form. Little is known about how the processing of miRNAs is modulated. Here we show that the RNA-binding protein DiGeorge critical region-8 (DGCR8), which is essential for the first processing step, is a heme-binding protein. The association with heme promotes dimerization of DGCR8. The heme-bound DGCR8 dimer seems to trimerize upon binding pri-miRNAs and is active in triggering pri-miRNA cleavage, whereas the heme-free monomer is much less active. A heme-binding region of DGCR8 inhibits the pri-miRNA-processing activity of the monomer. This putative autoinhibition is overcome by heme. Our finding that heme is involved in pri-miRNA processing suggests that the gene-regulation network of miRNAs and signal-transduction pathways involving heme might be connected.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, California 90095, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Faller
authors.forename: Michio
authors.initials: M
authors.lastname: Matsunaga
authors.forename: Sheng
authors.initials: S
authors.lastname: Yin
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
mesh_terms: D000595:Amino Acid Sequence; D019281:Dimerization; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006420:Hemeproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C474043:DGCR8 protein, human; D006420:Hemeproteins; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; D006418:Heme