title: A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain.
abstract: Argonaute (Ago) proteins mediate silencing of nucleic acid targets by small RNAs. In fission yeast, Ago1, Tas3 and Chp1 assemble into a RITS complex, which silences transcription near centromeres. Here we describe a repetitive motif within Tas3, termed the 'Argonaute hook', that is conserved from yeast to humans and binds Ago proteins through their PIWI domains in vitro and in vivo. Site-directed mutation of key residues in the motif disrupts Ago binding and heterochromatic silencing in vivo. Unexpectedly, a PIWI domain pocket that binds the 5' end of the short interfering RNA guide strand is required for direct binding of the Ago hook. Moreover, wild-type but not mutant Ago hook peptides derepress microRNA-mediated translational silencing of a target messenger RNA. Proteins containing the conserved Ago hook may thus be important regulatory components of effector complexes in RNA interference.
authors: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors: Susanne
authors: S
authors: Till
authors: Erwan
authors: E
authors: Lejeune
authors: Rolf
authors: R
authors: Thermann
authors: Miriam
authors: M
authors: Bortfeld
authors: Michael
authors: M
authors: Hothorn
authors: Daniel
authors: D
authors: Enderle
authors: Constanze
authors: C
authors: Heinrich
authors: Matthias W
authors: MW
authors: Hentze
authors: Andreas G
authors: AG
authors: Ladurner
mesh_terms: D000595:Amino Acid Sequence; D060565:Argonaute Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
chemical_list: C466422:AGO2 protein, human; C481643:Ago1 protein, S pombe; D060565:Argonaute Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C115018:Chp1 protein, S pombe; D015852:Eukaryotic Initiation Factor-2; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C499720:Tas3 protein, S pombe