title: The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division.
abstract: During the asymmetric division of Drosophila neuroblasts (NBs), the scaffold Miranda (Mira) coordinates the subcellular distribution of cell-fate determinants including Staufen (Stau) and segregates them into the ganglion mother cells (GMCs). Here we show the fifth double-stranded RNA (dsRNA)-binding domain (dsRBD5) of Stau is necessary and sufficient for binding to a coiled-coil region of Mira cargo-binding domain (CBD). The crystal structure of Mira514-595/Stau dsRBD5 complex illustrates that Mira forms an elongated parallel coiled-coil dimer, and two dsRBD5 symmetrically bind to the Mira dimer through their exposed β-sheet faces, revealing a previously unrecognized protein interaction mode for dsRBDs. We further demonstrate that the Mira-Stau dsRBD5 interaction is responsible for the asymmetric localization of Stau during Drosophila NB asymmetric divisions. Finally, we find the CBD-mediated dimer assembly is likely a common requirement for Mira to recognize and translocate other cargos including brain tumour (Brat).
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Key Laboratory of Molecular Medicine, Ministry of Education, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200433, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Key Laboratory of Molecular Medicine, Ministry of Education, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200433, China.|School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Zelin
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Key Laboratory of Molecular Medicine, Ministry of Education, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200433, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Key Laboratory of Molecular Medicine, Ministry of Education, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200433, China.|Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wen
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Key Laboratory of Molecular Medicine, Ministry of Education, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200433, China.
authors.forename: Wenning
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011487:Protein Conformation; D021381:Protein Transport / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C107613:Mira protein, Drosophila; D016601:RNA-Binding Proteins; C069927:stau protein, Drosophila