The YTH Domain is a Novel RNA Binding Domain

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Feb 20

PMID 20167602

Citations 168

Authors

Zhaiyi Zhang

Dominik Theler

Katarzyna H Kaminska

Michael Hiller

Pierre De La Grange

Rainer Pudimat

Ilona Rafalska

Bettina Heinrich

Janusz M Bujnicki

Frederic H-T Allain

Stefan Stamm

Affiliations

Soon will be listed here.

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.

Citing Articles

The role of N(6)-methyladenosine (m6a) modification in cancer: recent advances and future directions.

Xie X, Fang Z, Zhang H, Wang Z, Li J, Jia Y EXCLI J. 2025; 24:113-150.

PMID: 39967906 PMC: 11830918. DOI: 10.17179/excli2024-7935.

Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health.

Li P, Lin Y, Ma H, Zhang J, Zhang Q, Yan R Cell Death Discov. 2025; 11(1):43.

PMID: 39904996 PMC: 11794895. DOI: 10.1038/s41420-025-02324-z.

RNA Metabolism and the Role of Small RNAs in Regulating Multiple Aspects of RNA Metabolism.

Dawar P, Adhikari I, Mandal S, Jayee B Noncoding RNA. 2025; 11(1.

PMID: 39846679 PMC: 11755482. DOI: 10.3390/ncrna11010001.

The interplay between RNA m6A modification and radiation biology of cancerous and non-cancerous tissues: a narrative review.

Cheng Y, Shang Y, Zhang S, Fan S Cancer Biol Med. 2025; 21(12.

PMID: 39831771 PMC: 11745087. DOI: 10.20892/j.issn.2095-3941.2024.0415.

YTHDF1 Regulates RELA m6A Modification and Activates the NF-Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer.

Huang Y, Liang S, Li L, Zeng Q, Li B Cancer Med. 2025; 14(2):e70611.

PMID: 39821576 PMC: 11740084. DOI: 10.1002/cam4.70611.

References

Perez-Arellano I, Gallego J, Cervera J . The PUA domain - a structural and functional overview. FEBS J. 2007; 274(19):4972-84. DOI: 10.1111/j.1742-4658.2007.06031.x. View

Rafalska I, Zhang Z, Benderska N, Wolff H, Hartmann A, Brack-Werner R . The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation. Hum Mol Genet. 2004; 13(15):1535-49. DOI: 10.1093/hmg/ddh167. View

McPheeters D, Cremona N, Sunder S, Chen H, Averbeck N, Leatherwood J . A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions. Nat Struct Mol Biol. 2009; 16(3):255-64. PMC: 2776722. DOI: 10.1038/nsmb.1556. View

Stoss O, Olbrich M, Hartmann A, Konig H, Memmott J, Andreadis A . The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites. J Biol Chem. 2000; 276(12):8665-73. DOI: 10.1074/jbc.M006851200. View

Hargous Y, Hautbergue G, Tintaru A, Skrisovska L, Golovanov A, Stevenin J . Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8. EMBO J. 2006; 25(21):5126-37. PMC: 1630407. DOI: 10.1038/sj.emboj.7601385. View

Koradi R, Billeter M, Wuthrich K . MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph. 1996; 14(1):51-5, 29-32. DOI: 10.1016/0263-7855(96)00009-4. View

Li M, Rasulova F, Melnikov E, Rotanova T, Gustchina A, Maurizi M . Crystal structure of the N-terminal domain of E. coli Lon protease. Protein Sci. 2005; 14(11):2895-900. PMC: 2253230. DOI: 10.1110/ps.051736805. View

Auweter S, Oberstrass F, Allain F . Solving the structure of PTB in complex with pyrimidine tracts: an NMR study of protein-RNA complexes of weak affinities. J Mol Biol. 2007; 367(1):174-86. DOI: 10.1016/j.jmb.2006.12.053. View

Kurowski M, Bujnicki J . GeneSilico protein structure prediction meta-server. Nucleic Acids Res. 2003; 31(13):3305-7. PMC: 168964. DOI: 10.1093/nar/gkg557. View

10.

Harigaya Y, Tanaka H, Yamanaka S, Tanaka K, Watanabe Y, Tsutsumi C . Selective elimination of messenger RNA prevents an incidence of untimely meiosis. Nature. 2006; 442(7098):45-50. DOI: 10.1038/nature04881. View

11.

Bourgeois C, Lejeune F, Stevenin J . Broad specificity of SR (serine/arginine) proteins in the regulation of alternative splicing of pre-messenger RNA. Prog Nucleic Acid Res Mol Biol. 2004; 78:37-88. DOI: 10.1016/S0079-6603(04)78002-2. View

12.

Lie Y, Macdonald P . Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation. Development. 1999; 126(6):1129-38. DOI: 10.1242/dev.126.6.1129. View

13.

Auweter S, Fasan R, Reymond L, Underwood J, Black D, Pitsch S . Molecular basis of RNA recognition by the human alternative splicing factor Fox-1. EMBO J. 2005; 25(1):163-73. PMC: 1356361. DOI: 10.1038/sj.emboj.7600918. View

14.

White E, Ruley H . PUM2, a novel murine puf protein, and its consensus RNA-binding site. RNA. 2002; 7(12):1855-66. PMC: 1370223. View

15.

Zuker M . Prediction of RNA secondary structure by energy minimization. Methods Mol Biol. 1994; 25:267-94. DOI: 10.1385/0-89603-276-0:267. View

16.

Imai Y, Matsuo N, Ogawa S, Tohyama M, Takagi T . Cloning of a gene, YT521, for a novel RNA splicing-related protein induced by hypoxia/reoxygenation. Brain Res Mol Brain Res. 1998; 53(1-2):33-40. DOI: 10.1016/s0169-328x(97)00262-3. View

17.

Hertz G, Stormo G . Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics. 1999; 15(7-8):563-77. DOI: 10.1093/bioinformatics/15.7.563. View

18.

Auweter S, Oberstrass F, Allain F . Sequence-specific binding of single-stranded RNA: is there a code for recognition?. Nucleic Acids Res. 2006; 34(17):4943-59. PMC: 1635273. DOI: 10.1093/nar/gkl620. View

19.

Chen Y, Varani G . Protein families and RNA recognition. FEBS J. 2005; 272(9):2088-97. DOI: 10.1111/j.1742-4658.2005.04650.x. View

20.

Coulter L, Landree M, Cooper T . Identification of a new class of exonic splicing enhancers by in vivo selection. Mol Cell Biol. 1997; 17(4):2143-50. PMC: 232062. DOI: 10.1128/MCB.17.4.2143. View