title: The YTH domain is a novel RNA binding domain.
abstract: The YTH (YT521-B homology) domain was identified by sequence comparison and is found in 174 different proteins expressed in eukaryotes. It is characterized by 14 invariant residues within an alpha-helix/beta-sheet structure. Here we show that the YTH domain is a novel RNA binding domain that binds to a short, degenerated, single-stranded RNA sequence motif. The presence of the binding motif in alternative exons is necessary for YT521-B to directly influence splice site selection in vivo. Array analyses demonstrate that YT521-B predominantly regulates vertebrate-specific exons. An NMR titration experiment identified the binding surface for single-stranded RNA on the YTH domain. Structural analyses indicate that the YTH domain is related to the pseudouridine synthase and archaeosine transglycosylase (PUA) domain. Our data show that the YTH domain conveys RNA binding ability to a new class of proteins that are found in all eukaryotic organisms.
authors.affiliation: Institute for Biochemistry, Universität Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany.
authors.forename: Zhaiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dominik
authors.initials: D
authors.lastname: Theler
authors.forename: Katarzyna H
authors.initials: KH
authors.lastname: Kaminska
authors.forename: Michael
authors.initials: M
authors.lastname: Hiller
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.forename: Rainer
authors.initials: R
authors.lastname: Pudimat
authors.forename: Ilona
authors.initials: I
authors.lastname: Rafalska
authors.forename: Bettina
authors.initials: B
authors.lastname: Heinrich
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
mesh_terms: D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C490769:YTHDC1 protein, human; D012313:RNA