The YTH Domain Is a Novel RNA Binding Domain

• Published in: The Journal of biological chemistry 2010-05, Vol.285 (19), p.14701-14710
• Main Authors: Zhang, Zhaiyi, Theler, Dominik, Kaminska, Katarzyna H., Hiller, Michael, de la Grange, Pierre, Pudimat, Rainer, Rafalska, Ilona, Heinrich, Bettina, Bujnicki, Janusz M., Allain, Frédéric H.-T., Stamm, Stefan
• Format: Article
• Language: English
• Subjects: Binding Sites; Biomarkers - metabolism; Gene Expression Profiling; Gene Regulation; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Nerve Tissue Proteins - genetics; NMR; Oligonucleotide Array Sequence Analysis; Protein Conformation; Protein Folding; Protein Structure, Tertiary; RNA; RNA - genetics; RNA - metabolism; RNA Processing; RNA Splicing; RNA Splicing - physiology; RNA Splicing Factors; RNA-binding Protein; RNA-Binding Proteins - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.104711

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 α-helix/β-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.