Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity

Nature Structural and Molecular Biology

Volumn 23, Issue 5, 2016, Pages 426-433

  Matthews, Melissa M ^a   Thomas, Justin M ^a   Zheng, Yuxuan ^a   Tran, Kiet ^a   Phelps, Kelly J ^a   Scott, Anna I ^a   Havel, Jocelyn ^a   Fisher, Andrew J ^a   Beal, Peter A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE DEAMINASE; ADENOSINE DEAMINASES ACTING ON RNA 2; DOUBLE STRANDED RNA; UNCLASSIFIED DRUG; ADARB1 PROTEIN, HUMAN; PROTEIN BINDING; RNA BINDING PROTEIN;

ARTICLE; BASE FLIPPING; CRYSTAL STRUCTURE; DEAMINATION; ENZYME ACTIVE SITE; HUMAN; PRIORITY JOURNAL; PROTEIN RNA BINDING; RNA CONFORMATION; RNA STRUCTURE; SITE DIRECTED MUTAGENESIS; BIOCATALYSIS; CHEMISTRY; ENZYME SPECIFICITY; HYDROGEN BOND; KINETICS; MOLECULAR MODEL; NUCLEOTIDE SEQUENCE; X RAY CRYSTALLOGRAPHY;

ADENOSINE DEAMINASE; BASE SEQUENCE; BIOCATALYSIS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; HUMANS; HYDROGEN BONDING; KINETICS; MODELS, MOLECULAR; PROTEIN BINDING; RNA, DOUBLE-STRANDED; RNA-BINDING PROTEINS; SUBSTRATE SPECIFICITY;

EID: 84963603761     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3203     Document Type: Article

References (44)

1. Grosjean, H. Fine-Tuning of RNA Functions by Modification and Editing (Springer, 2005).
2. Bass, B.L. RNA editing by adenosine deaminases that act on RNA. Annu. Rev. Biochem. 71, 817-846 (2002).
3. Nishikura, K. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 79, 321-349 (2010).
4. Wang, Q. et al. ADAR1 regulates ARHGAP26 gene expression through RNA editing by disrupting miR-30b-3p and miR-573 binding. RNA 19, 1525-1536 (2013).
5. Rueter, S.M., Dawson, T.R. & Emeson, R.B. Regulation of alternative splicing by RNA editing. Nature 399, 75-80 (1999).
6. Yeo, J., Goodman, R.A., Schirle, N.T., David, S.S. & Beal, P.A. RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1. Proc. Natl. Acad. Sci. USA 107, 20715-20719 (2010).
7. Bass, B.L. et al. A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3, 947-949 (1997).
8. Maas, S., Kawahara, Y., Tamburro, K.M. & Nishikura, K. A-to-I RNA editing and human disease. RNA Biol. 3, 1-9 (2006).
9. Slotkin, W. & Nishikura, K. Adenosine-to-inosine RNA editing and human disease. Genome Med. 5, 105 (2013).
10. Morabito, M.V. et al. Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader-Willi syndrome. Neurobiol. Dis. 39, 169-180 (2010).
11. Rice, G.I. et al. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat. Genet. 44, 1243-1248 (2012).
12. Miyamura, Y. et al. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am. J. Hum. Genet. 73, 693-699 (2003).
13. Zhang, X.J. et al. Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH). Hum. Mutat. 23, 629-630 (2004).
14. Chen, L. et al. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat. Med. 19, 209-216 (2013).
15. Gallo, A. RNA editing enters the limelight in cancer. Nat. Med. 19, 130-131 (2013).
16. Shimokawa, T. et al. RNA editing of the GLI1 transcription factor modulates the output of Hedgehog signaling. RNA Biol. 10, 321-333 (2013).
17. Goodman, R.A., Macbeth, M.R. & Beal, P.A. ADAR proteins: structure and catalytic mechanism. Curr. Top. Microbiol. Immunol. 353, 1-33 (2012).
18. Li, J.B. et al. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science 324, 1210-1213 (2009).
19. Haudenschild, B.L. et al. A transition state analogue for an RNA-editing reaction. J. Am. Chem. Soc. 126, 11213-11219 (2004).
20. Phelps, K.J. et al. Recognition of duplex RNA by the deaminase domain of the RNA editing enzyme ADAR2. Nucleic Acids Res. 43, 1123-1132 (2015).
21. Macbeth, M.R. et al. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309, 1534-1539 (2005).
22. Kuttan, A. & Bass, B.L. Mechanistic insights into editing-site specificity of ADARs. Proc. Natl. Acad. Sci. USA 109, E3295-E3304 (2012).
23. Wong, S.K., Sato, S. & Lazinski, D.W. Substrate recognition by ADAR1 and ADAR2. RNA 7, 846-858 (2001).
24. Klimasauskas, S., Kumar, S., Roberts, R.J. & Cheng, X. HhaI methyltransferase flips its target base out of the DNA helix. Cell 76, 357-369 (1994).
25. Daujotyte, D. et al. HhaI DNA methyltransferase uses the protruding Gln237 for active flipping of its target cytosine. Structure 12, 1047-1055 (2004).
26. Thiyagarajan, S., Rajan, S.S. & Gautham, N. Cobalt hexammine induced tautomeric shift in Z-DNA: the structure of d(CGCGCA) d(TGCGCG) in two crystal forms. Nucleic Acids Res. 32, 5945-5953 (2004).
27. Slupphaug, G. et al. A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 384, 87-92 (1996).
28. Bruner, S.D., Norman, D.P. & Verdine, G.L. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403, 859-866 (2000).
29. Lau, A.Y., Schärer, O.D., Samson, L., Verdine, G.L. & Ellenberger, T. Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision. Cell 95, 249-258 (1998).
30. Brooks, S.C., Adhikary, S., Rubinson, E.H. & Eichman, B.F. Recent advances in the structural mechanisms of DNA glycosylases. Biochim. Biophys. Acta 1834, 247-271 (2013).
31. Eifler, T., Pokharel, S. & Beal, P.A. RNA-Seq analysis identifies a novel set of editing substrates for human ADAR2 present in Saccharomyces cerevisiae. Biochemistry 52, 7857-7869 (2013).
32. Eggington, J.M., Greene, T. & Bass, B.L. Predicting sites of ADAR editing in double-stranded RNA. Nat. Commun. 2, 319 (2011).
33. Peacock, H., Maydanovych, O. & Beal, P.A. N2-Modified 2-aminopurine ribonucleosides as minor-groove-modulating adenosine replacements in duplex RNA. Org. Lett. 12, 1044-1047 (2010).
34. Roberts, R.J. & Cheng, X. Base flipping. Annu. Rev. Biochem. 67, 181-198 (1998).
35. Hoang, C. & Ferré-D'Amaré, A.R. Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107, 929-939 (2001).
36. Parikh, S.S. et al. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 17, 5214-5226 (1998).
37. Yang, X., Gérczei, T., Glover, L.T. & Correll, C.C. Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping. Nat. Struct. Biol. 8, 968-973 (2001).
38. Carter, A.P. et al. Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science 291, 498-501 (2001).
39. Réblová, K. et al. Structure, dynamics, and elasticity of free 16s rRNA helix 44 studied by molecular dynamics simulations. Biopolymers 82, 504-520 (2006).
40. Xie, W., Liu, X. & Huang, R.H. Chemical trapping and crystal structure of a catalytic tRNA guanine transglycosylase covalent intermediate. Nat. Struct. Biol. 10, 781-788 (2003).
41. Erion, M.D. & Reddy, M.R. Calculation of relative hydration free energy differences for heteroaromatic compounds: use in the design of adenosine deaminase and cytidine deaminase inhibitors. J. Am. Chem. Soc. 120, 3295-3304 (1998).
42. Stefl, R. et al. The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove. Cell 143, 225-237 (2010).
43. Fierro-Monti, I. & Mathews, M.B. Proteins binding to duplexed RNA: one motif, multiple functions. Trends Biochem. Sci. 25, 241-246 (2000).
44. Mannion, N.M. et al. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep. 9, 1482-1494 (2014).