title: An extended dsRBD with a novel zinc-binding motif mediates nuclear retention of fission yeast Dicer.
abstract: Dicer proteins function in RNA interference (RNAi) pathways by generating small RNAs (sRNAs). Here, we report the solution structure of the C-terminal domain of Schizosaccharomyces pombe Dicer (Dcr1). The structure reveals an unusual double-stranded RNA binding domain (dsRBD) fold embedding a novel zinc-binding motif that is conserved among dicers in yeast. Although the C-terminal domain of Dcr1 still binds nucleic acids, this property is dispensable for proper functioning of Dcr1. In contrast, disruption of zinc coordination renders Dcr1 mainly cytoplasmic and leads to remarkable changes in gene expression and loss of heterochromatin assembly. In summary, our results reveal novel insights into the mechanism of nuclear retention of Dcr1 and raise the possibility that this new class of dsRBDs might generally function in nucleocytoplasmic trafficking and not substrate binding. The C-terminal domain of Dcr1 constitutes a novel regulatory module that might represent a potential target for therapeutic intervention with fungal diseases.
authors.affiliation: Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Barraud
authors.forename: Stephan
authors.initials: S
authors.lastname: Emmerth
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Hotz
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
authors.forename: Marc
authors.initials: M
authors.lastname: Bühler
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000201:enzymology*; D042002:Chromatin Assembly and Disassembly; D004722:Endoribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012330:RNA, Double-Stranded / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C568524:Dcr1 protein, S pombe; D004722:Endoribonucleases; D043244:Ribonuclease III; D015032:Zinc