title: Structure of Human DROSHA.
abstract: MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: S Chul
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Tuan Anh
authors.initials: TA
authors.lastname: Nguyen
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Yeon-Gil
authors.initials: YG
authors.lastname: Choi
authors.affiliation: Department of Physics and Astronomy, Seoul National University, Seoul 08826, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 08826, Korea; Institute of Applied Physics, Seoul National University, Seoul 08826, Korea.
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Jo
authors.affiliation: Department of Physics and Astronomy, Seoul National University, Seoul 08826, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 08826, Korea; Institute of Applied Physics, Seoul National University, Seoul 08826, Korea; Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea.
authors.forename: Sungchul
authors.initials: S
authors.lastname: Hohng
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. Electronic address: narrykim@snu.ac.kr.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. Electronic address: jaesungwoo@snu.ac.kr.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Woo
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: C474043:DGCR8 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases