Asymmetric dimethylarginine (aDMA) marks are placed on histones and the C-terminal domain (CTD) of RNA Polymerase II (RNAP II) and serve as a signal for recruitment of appropriate transcription and processing factors in coordination with transcription cycle. In contrast to other Tudor domain-containing proteins, Tudor domain-containing protein 3 (TDRD3) associates selectively with the aDMA marks but not with other methylarginine motifs. Here, we report the solution structure of the Tudor domain of TDRD3 bound to the asymmetrically dimethylated CTD. The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark. The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue. Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.

CEITEC Central European Institute of Technology Masaryk University CZ 62500 Brno Czech Republic

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Bedford MT, Richard S. Arginine methylation an emerging regulator of protein function. Mol. Cell. 2005;18:263–272. PubMed

Bedford MT, Clarke SG. Protein arginine methylation in mammals: who, what, and why. Mol. Cell. 2009;33:1–13. PubMed PMC

Siomi MC, Mannen T, Siomi H. How does the royal family of Tudor rule the PIWI-interacting RNA pathway? Genes Dev. 2010;24:636–646. PubMed PMC

Yang Y, Lu Y, Espejo A, Wu J, Xu W, Liang S, Bedford MT. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol. Cell. 2010;40:1016–1023. PubMed PMC

Sims RJ, 3rd, Rojas LA, Beck D, Bonasio R, Schuller R, Drury WJ, 3rd, Eick D, Reinberg D. The C-terminal domain of RNA polymerase II is modified by site-specific methylation. Science. 2011;332:99–103. PubMed PMC

Phatnani HP, Greenleaf AL. Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev. 2006;20:2922–2936. PubMed

Corden JL. Transcription. Seven ups the code. Science. 2007;318:1735–1736. PubMed

Chapman RD, Heidemann M, Hintermair C, Eick D. Molecular evolution of the RNA polymerase II CTD. Trends Genet. 2008;24:289–296. PubMed

Egloff S, Murphy S. Cracking the RNA polymerase II CTD code. Trends Genet. 2008;24:280–288. PubMed

Buratowski S. The CTD code. Nat. Struct. Biol. 2003;10:679–680. PubMed

Buratowski S. Progression through the RNA polymerase II CTD cycle. Mol. Cell. 2009;36:541–546. PubMed PMC

Hirose Y, Manley JL. RNA polymerase II and the integration of nuclear events. Genes Dev. 2000;14:1415–1429. PubMed

Maniatis T, Reed R. An extensive network of coupling among gene expression machines. Nature. 2002;416:499–506. PubMed

Meinhart A, Kamenski T, Hoeppner S, Baumli S, Cramer P. A structural perspective of CTD function. Genes Dev. 2005;19:1401–1415. PubMed

Viladevall L, St Amour CV, Rosebrock A, Schneider S, Zhang C, Allen JJ, Shokat KM, Schwer B, Leatherwood JK, Fisher RP. TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol. Cell. 2009;33:738–751. PubMed PMC

Ghosh A, Shuman S, Lima CD. Structural insights to how mammalian capping enzyme reads the CTD code. Mol. Cell. 2011;43:299–310. PubMed PMC

de la Mata M, Kornblihtt AR. RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. Nat. Struct. Mol. Biol. 2006;13:973–980. PubMed

Munoz MJ, de la Mata M, Kornblihtt AR. The carboxy terminal domain of RNA polymerase II and alternative splicing. Trends Biochem. Sci. 2010;35:497–504. PubMed

David CJ, Boyne AR, Millhouse SR, Manley JL. The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes Dev. 2011;25:972–983. PubMed PMC

de Almeida SF, Grosso AR, Koch F, Fenouil R, Carvalho S, Andrade J, Levezinho H, Gut M, Eick D, Gut I, et al. Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36. Nat. Struct. Mol. Biol. 2011;18:977–983. PubMed

Ahn SH, Kim M, Buratowski S. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3′ end processing. Mol. Cell. 2004;13:67–76. PubMed

Egloff S, O'Reilly D, Chapman RD, Taylor A, Tanzhaus K, Pitts L, Eick D, Murphy S. Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science. 2007;318:1777–1779. PubMed PMC

Johnson SA, Kim H, Erickson B, Bentley DL. The export factor Yra1 modulates mRNA 3′ end processing. Nat. Struct. Mol. Biol. 2011;18:1164–1171. PubMed PMC

MacKellar AL, Greenleaf AL. Cotranscriptional association of mRNA export factor Yra1 with C-terminal domain of RNA polymerase II. J. Biol. Chem. 2011;286:36385–36395. PubMed PMC

Liu K, Guo Y, Liu H, Bian C, Lam R, Liu Y, Mackenzie F, Rojas LA, Reinberg D, Bedford MT, et al. Crystal structure of TDRD3 and methyl-arginine binding characterization of TDRD3, SMN and SPF30. PLoS One. 2012;7:e30375. PubMed PMC

Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M. Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat. Struct. Mol. Biol. 2011;18:1414–1420. PubMed

Liu K, Chen C, Guo Y, Lam R, Bian C, Xu C, Zhao DY, Jin J, MacKenzie F, Pawson T, et al. Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. Proc. Natl Acad. Sci. USA. 2010;107:18398–18403. PubMed PMC

Liu H, Wang JY, Huang Y, Li Z, Gong W, Lehmann R, Xu RM. Structural basis for methylarginine-dependent recognition of Aubergine by Tudor. Genes Dev. 2010;24:1876–1881. PubMed PMC

Cote J, Richard S. Tudor domains bind symmetrical dimethylated arginines. J. Biol. Chem. 2005;280:28476–28483. PubMed

Chen C, Jin J, James DA, Adams-Cioaba MA, Park JG, Guo Y, Tenaglia E, Xu C, Gish G, Min J, et al. Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc. Natl Acad. Sci. USA. 2009;106:20336–20341. PubMed PMC

Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR. 1995;6:277–293. PubMed

Bax A, Grzesiek S. Methodological advances in protein NMR. Accounts Chem. Res. 1993;26:131–138.

Peterson RD, Theimer CA, Wu H, Feigon J. New applications of 2D filtered/edited NOESY for assignment and structure elucidation of RNA and RNA-protein complexes. J. Biomol. NMR. 2004;28:59–67. PubMed

Zwahlen C, Legault P, Vincent SJF, Greenblatt J, Konrat R, Kay LE. Methods for measurement of intermolecular NOEs by multinuclear NMR spectroscopy: Application to a bacteriophage lambda N-peptide/boxB RNA complex. J. Am. Chem. Soc. 1997;119:6711–6721.

Guntert P. Automated NMR structure calculation with CYANA. Methods Mol. Biol. 2004;278:353–378. PubMed

Herrmann T, Guntert P, Wuthrich K. Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. J. Mol. Biol. 2002;319:209–227. PubMed

Case DA, Darden TA, Cheatham TE, III, Simmerling CL, Wang J, Duke RE, Luo R, Crowley M, Walker RC, Zhang W, et al. AMBER 10. San Francisco: University of California; 2008.

Case DA, Cheatham TE, 3rd, Darden T, Gohlke H, Luo R, Merz KM, Jr, Onufriev A, Simmerling C, Wang B, Woods RJ. The Amber biomolecular simulation programs. J. Comput. Chem. 2005;26:1668–1688. PubMed PMC

Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA. A 2nd generation force-field for the simulation of proteins, nucleic-acids, and organic-molecules. J. Am. Chem. Soc. 1995;117:5179–5197.

Bayly CI, Cieplak P, Cornell WD, Kollman PA. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges - the Resp Model. J. Phys. Chem. 1993;97:10269–10280.

Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R, Thornton JM. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J. Biomol. NMR. 1996;8:477–486. PubMed

Vriend G. What If - a molecular modeling and drug design program. J. Mol. Graphics. 1990;8:52–56. PubMed

Heyduk T, Lee JC. Application of fluorescence energy transfer and polarization to monitor Escherichia coli cAMP receptor protein and lac promoter interaction. Proc. Natl Acad. Sci. USA. 1990;87:1744–1748. PubMed PMC

Grimme S, Antony J, Ehrlich S, Krieg H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J. Chem. Phys. 2010;132:154104. PubMed

Tao J, Perdew JP, Staroverov VN, Scuseria GE. Climbing the density functional ladder: nonempirical meta-generalized gradient approximation designed for molecules and solids. Phys. Rev. Lett. 2003;91:146401. PubMed

Turney JM, Simmonett AC, Parrish RM, Hohenstein EG, Evangelista FA, Fermann JT, Mintz BJ, Burns LA, Wilke JJ, Abrams ML, et al. Psi4: an open-source ab initio electronic structure program. WIREs: Comput. Mol. Sci. 2012;2:556–565.

Luisi B, Orozco M, Sponer J, Luque FJ, Shakked Z. On the potential role of the amino nitrogen atom as a hydrogen bond acceptor in macromolecules. J. Mol. Biol. 1998;279:1123–1136. PubMed

Jeziorski B, Moszynski R, Szalewicz K. Perturbation-theory approach to intermolecular potential-energy surfaces of Van-Der-Waals complexes. Chem. Rev. 1994;94: 1887–1930.

Cubero E, Luque FJ, Orozco M. Is polarization important in cation-pi interactions? Proc. Natl Acad. Sci. USA. 1998;95:5976–5980. PubMed PMC

Kim D, Hu S, Tarakeshwar P, Kim KS, Lisy JM. Cation-pi interactions: A theoretical investigation of the interaction of metallic and organic cations with alkenes, arenes, and heteroarenes. J. Phys. Chem. A. 2003;107:1228–1238.

Zobrazit více v PubMed

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