Institute for Biochemistry, Universität Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany.
J Biol Chem. 2010 May 7;285(19):14701-10. doi: 10.1074/jbc.M110.104711. Epub 2010 Feb 18.
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.
YTH(YT521-B 同源性)结构域是通过序列比较鉴定的,存在于真核生物表达的 174 种不同蛋白质中。它的特征是在一个α-螺旋/β-折叠结构中有 14 个不变残基。在这里,我们表明 YTH 结构域是一个新的 RNA 结合结构域,它可以与一个短的、简并的、单链 RNA 序列基序结合。在替代外显子中存在结合基序对于 YT521-B 直接影响体内剪接位点选择是必要的。阵列分析表明,YT521-B 主要调节脊椎动物特异性外显子。NMR 滴定实验确定了 YTH 结构域上结合单链 RNA 的结合表面。结构分析表明,YTH 结构域与假尿嘧啶核苷合酶和古核嘧啶核苷转糖苷酶(PUA)结构域有关。我们的数据表明,YTH 结构域赋予了一类新的蛋白质 RNA 结合能力,这些蛋白质存在于所有真核生物中。