title: Solution structure of the second RNA recognition motif (RRM) domain of murine T cell intracellular antigen-1 (TIA-1) and its RNA recognition mode.
abstract: T cell intracellular antigen-1 (TIA-1), an apoptosis promoting factor, functions as a splicing regulator for the Fas pre-mRNA. TIA-1 possesses three RNA recognition motifs (RRMs) and a glutamine-rich domain. The second RRM (RRM2) is necessary and sufficient for tight, sequence-specific binding to the uridine-rich sequences buried around the 5' splice sites. In the present study, we solved the solution structure of the murine TIA-1 RRM2 by heteronuclear-nuclear magnetic resonance spectroscopy. The TIA-1 RRM2 adopts the RRM fold (betaalphabetabetaalphabeta) and possesses an extra beta-strand between beta2 and beta3, which forms an additional beta-sheet with the C-terminal part of beta2. We refer to this structure as the beta2-beta2' beta-loop. Interestingly, this characteristic beta-loop structure is conserved among a number of RRMs, including the U2AF65 RRM2 and the Sex-lethal RRM1 and RRM2, which also bind to uridine-rich RNAs. Furthermore, we identified a new sequence motif in the beta2-beta2' beta-loop, the DxxT motif. Chemical shift perturbation analyses of both the main and side chains upon binding to the uridine pentamer RNA revealed that most of the beta-sheet surface, including the beta2-beta2' beta-loop, is involved in the RNA binding. An investigation of the chemical shift perturbation revealed similarity in the RNA recognition modes between the TIA-1 and U2AF65 RRMs.
authors.affiliation: Protein Research Group, Genomic Sciences Center, Yokohama Institute, RIKEN, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Kuwasako
authors.forename: Mari
authors.initials: M
authors.lastname: Takahashi
authors.forename: Naoya
authors.initials: N
authors.lastname: Tochio
authors.forename: Chikage
authors.initials: C
authors.lastname: Abe
authors.forename: Kengo
authors.initials: K
authors.lastname: Tsuda
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Taguchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Muto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D012996:Solutions; D000072668:Splicing Factor U2AF; D013499:Surface Properties; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D012996:Solutions; D000072668:Splicing Factor U2AF; D000074019:T-Cell Intracellular Antigen-1; C499367:Tia1 protein, mouse; C000607494:U2AF2 protein, human; C000607495:Zrsr1 protein, mouse