title: Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions.
abstract: Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the translation of target mRNAs, and participates in the maintenance of cell 'stemness' and tumorigenesis. Msi1 reportedly binds to the 3'-untranslated region of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of its translation by competing with eIF4G for PABP binding, resulting in triggering of Notch signaling. Here, the mechanism by which Msi1 recognizes the target RNA sequence using its Ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1 and RBD2 has been revealed on identification of the minimal binding RNA for each RBD and determination of the three-dimensional structure of the RBD1:RNA complex. Unique interactions were found for the recognition of the target sequence by Msi1 RBD1: adenine is sandwiched by two phenylalanines and guanine is stacked on the tryptophan in the loop between β1 and α1. The minimal recognition sequences that we have defined for Msi1 RBD1 and RBD2 have actually been found in many Msi1 target mRNAs reported to date. The present study provides molecular clues for understanding the biology involving Musashi family proteins.
authors.affiliation: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ohyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagata
authors.forename: Kengo
authors.initials: K
authors.lastname: Tsuda
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takao
authors.initials: T
authors.lastname: Imai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Masato
authors.initials: M
authors.lastname: Katahira
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D051379:Mice; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D024322:Amino Acids, Aromatic; C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012313:RNA