PMID- 26748718 OWN - NLM STAT- MEDLINE DCOM- 20160531 LR - 20170915 IS - 1097-4172 (Electronic) IS - 0092-8674 (Linking) VI - 164 IP - 1-2 DP - 2016 Jan 14 TI - Structure of Human DROSHA. PG - 81-90 LID - S0092-8674(15)01643-8 [pii] LID - 10.1016/j.cell.2015.12.019 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Kwon, S Chul AU - Kwon SC AD - Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. FAU - Nguyen, Tuan Anh AU - Nguyen TA AD - Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. FAU - Choi, Yeon-Gil AU - Choi YG AD - Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. FAU - Jo, Myung Hyun AU - Jo MH AD - 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. FAU - Hohng, Sungchul AU - Hohng S AD - 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. FAU - Kim, V Narry AU - Kim VN AD - 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. FAU - Woo, Jae-Sung AU - Woo JS AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151231 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DGCR8 protein, human) RN - 0 (MicroRNAs) RN - 0 (RNA-Binding Proteins) RN - EC 3.1.26.3 (DICER1 protein, human) RN - EC 3.1.26.3 (DROSHA protein, human) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM CIN - Cell Res. 2016 May;26(5):511-2. PMID: 27125999 MH - Amino Acid Sequence MH - Crystallography, X-Ray MH - DEAD-box RNA Helicases/chemistry/metabolism MH - Evolution, Molecular MH - Humans MH - MicroRNAs/chemistry/*metabolism MH - Models, Chemical MH - Models, Molecular MH - Molecular Sequence Data MH - Nucleic Acid Conformation MH - Protein Folding MH - Protein Structure, Tertiary MH - *RNA Processing, Post-Transcriptional MH - RNA-Binding Proteins/metabolism MH - Ribonuclease III/*chemistry/genetics/metabolism MH - Sequence Alignment MH - Structural Homology, Protein EDAT- 2016/01/11 06:00 MHDA- 2016/06/01 06:00 CRDT- 2016/01/11 06:00 PHST- 2015/11/05 00:00 [received] PHST- 2015/11/28 00:00 [revised] PHST- 2015/12/07 00:00 [accepted] PHST- 2016/01/11 06:00 [entrez] PHST- 2016/01/11 06:00 [pubmed] PHST- 2016/06/01 06:00 [medline] AID - S0092-8674(15)01643-8 [pii] AID - 10.1016/j.cell.2015.12.019 [doi] PST - ppublish SO - Cell. 2016 Jan 14;164(1-2):81-90. doi: 10.1016/j.cell.2015.12.019. Epub 2015 Dec 31.