Native Tertiary Structure and Nucleoside Modifications Suppress tRNA's Intrinsic Ability to Activate the Innate Immune Sensor PKR

PLoS ONE

Volumn 8, Issue 3, 2013, Pages

  Nallagatla, Subba Rao ^a,d   Jones, Christie N ^b,e   Ghosh, Saikat Kumar B ^a   Sharma, Suresh D ^c   Cameron, Craig E ^c   Spremulli, Linda L ^b   Bevilacqua, Philip C ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b University of North Carolina at Chapel Hill   (United States)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

^d AuraSense Therapeutics   (United States)

^e TRINITY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOSIDE; PROTEIN KINASE R; TRANSFER RNA;

ANIMAL TISSUE; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; COW; DIMERIZATION; ENZYME ACTIVATION; ESCHERICHIA COLI; GEL MOBILITY SHIFT ASSAY; IN VITRO STUDY; IN VIVO STUDY; LIVER; MUTANT; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PURIFICATION; RNA PURIFICATION; RNA STRUCTURE; WHEAT; YEAST;

ANIMALS; BASE SEQUENCE; CATTLE; CELL LINE, TUMOR; DIMERIZATION; EIF-2 KINASE; ENZYME ACTIVATION; HUMANS; IMMUNITY, INNATE; MOLECULAR SEQUENCE DATA; MUTATION; NUCLEIC ACID CONFORMATION; NUCLEOSIDES; PROTEIN BINDING; RNA; RNA, TRANSFER; SACCHAROMYCES CEREVISIAE;

EID: 84874612971     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0057905     Document Type: Article

References (67)

1. Nallagatla SR, Toroney R, Bevilacqua PC, (2011) Regulation of innate immunity through RNA structure and the protein kinase PKR. Curr Opin Struct Biol 21: 119-127.
2. Yoneyama M, Fujita T, (2009) Recognition of viral nucleic acids in innate immunity. Rev Med Virol 20: 4-22.
3. Cole JL, (2007) Activation of PKR: an open and shut case? Trends Biochem Sci 32: 57-62.
4. Sadler AJ, (2010) Orchestration of the activation of protein kinase R by the RNA-binding motif. J Interferon Cytokine Res 30: 195-204.
5. Bevilacqua PC, Cech TR, (1996) Minor-groove recognition of double-stranded RNA by the double-stranded RNA-binding domain from the RNA-activated protein kinase PKR. Biochemistry 35: 9983-9994.
6. Ryter JM, Schultz SC, (1998) Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA. EMBO J 17: 7505-7513.
7. Dar AC, Dever TE, Sicheri F, (2005) Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR. Cell 122: 887-900.
8. Dey M, Cao C, Dar AC, Tamura T, Ozato K, et al. (2005) Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition. Cell 122: 901-913.
9. Lemaire PA, Lary J, Cole JL, (2005) Mechanism of PKR activation: dimerization and kinase activation in the absence of double-stranded RNA. J Mol Biol 345: 81-90.
10. Heinicke LA, Wong CJ, Lary J, Nallagatla SR, Diegelman-Parente A, et al. (2009) RNA dimerization promotes PKR dimerization and activation. J Mol Biol 390: 319-338.
11. Heinicke L, Bevilacqua PC, (2012) Activation of PKR by RNA misfolding: The HDV ribozyme dimerizes to activate PKR. RNA 18: 2157-2165.
12. Lemaire PA, Anderson E, Lary J, Cole JL, (2008) Mechanism of PKR activation by dsRNA. J Mol Biol 381: 351-360.
13. VanOudenhove J, Anderson E, Krueger S, Cole JL, (2009) Analysis of PKR structure by small-angle scattering. J Mol Biol 387: 910-920.
14. Pindel A, Sadler A (2010) The role of protein kinase R in the interferon response. J Interferon Cytokine Res. 31, 59-70.
15. Garcia MA, Gil J, Ventoso I, Guerra S, Domingo E, et al. (2006) Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev 70: 1032-1060.
16. Garcia MA, Meurs EF, Esteban M, (2007) The dsRNA protein kinase PKR: Virus and cell control. Biochimie 89: 799-811.
17. Sadler AJ, Williams BR, (2007) Structure and function of the protein kinase R. Curr Top Microbiol Immunol. 316: 253-292.
18. Peel AL, Rao RV, Cottrell BA, Hayden MR, Ellerby LM, et al. (2001) Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue. Hum Mol Genet 10: 1531-1538.
19. Bullido MJ, Martinez-Garcia A, Tenorio R, Sastre I, Munoz DG, et al. (2007) Double stranded RNA activated EIF2 alpha kinase (EIF2AK2; PKR) is associated with Alzheimer's disease. Neurobiol Aging 8: 1160-1166.
20. Morel M, Couturier J, Lafay-Chebassier C, Paccalin M, Page G, (2009) PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's disease. J Cell Mol Med. 8A: 1476-1488.
21. Mouton-Liger F, Paquet C, Dumurgier J, Bouras C, Pradier L, et al. (2012) Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2alpha pathway. Biochim Biophys Acta. 6: 885-896.
22. Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, et al. (2010) Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140: 338-348.
23. Nallagatla SR, Toroney R, Bevilacqua PC, (2008) A brilliant disguise for self RNA: 5'-end and internal modifications of primary transcripts suppress elements of innate immunity. RNA Biol 5: 25-29.
24. Ben-Asouli Y, Banai Y, Pel-Or Y, Shir A, Kaempfer R, (2002) Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 108: 221-232.
25. Cohen-Chalamish S, Hasson A, Weinberg D, Namer LS, Banai Y, et al. (2009) Dynamic refolding of IFN-gamma mRNA enables it to function as PKR activator and translation template. Nat Chem Biol 5: 896-903.
26. Heinicke LA, Nallagatla SR, Hull CM, Bevilacqua PC, (2011) RNA helical imperfections regulate activation of the protein kinase PKR: effects of bulge position, size, and geometry. RNA 17: 957-966.
27. Nallagatla SR, Hwang J, Toroney R, Zheng X, Cameron CE, et al. (2007) 5′-triphosphate-dependent activation of PKR by RNAs with short stem-loops. Science 318: 1455-1458.
28. Toroney R, Hull CM, Sokoloski J, Bevilacqua PC, (2012) Mechanistic characterization of the 5′-triphosphate-dependent activation of PKR: Lack of 5′-end nucleobase specificity, evidence for a distinct triphosphate binding site, and a critical role for the dsRBD. RNA 18: 1862-1874.
29. Dauber B, Martinez-Sobrido L, Schneider J, Hai R, Waibler Z, et al. (2009) Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog 5: e1000473.
30. Nallagatla SR, Bevilacqua PC, (2008) Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. RNA 14: 1201-1213.
31. Anderson BR, Muramatsu H, Nallagatla SR, Bevilacqua PC, Sansing LH, et al. (2010) Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res 38: 5884-5892.
32. Shimoike T, McKenna SA, Lindhout DA, Puglisi JD, (2009) Translational insensitivity to potent activation of PKR by HCV IRES RNA. Antiviral Res 83: 228-237.
33. Toroney R, Nallagatla SR, Boyer JA, Cameron CE, Bevilacqua PC, (2010) Regulation of PKR by HCV IRES RNA: importance of domain II and NS5A. J Mol Biol 400: 393-412.
34. Davis S, Watson JC, (1996) In vitro activation of the interferon-induced, double-stranded RNA-dependent protein kinase PKR by RNA from the 3′ untranslated regions of human alpha-tropomyosin. Proc Natl Acad Sci U S A 93: 508-513.
35. Nussbaum JM, Gunnery S, Mathews MB, (2002) The 3'-untranslated regions of cytoskeletal muscle mRNAs inhibit translation by activating the double-stranded RNA-dependent protein kinase PKR. Nucleic Acids Res 30: 1205-1212.
36. Huichalaf C, Sakai K, Jin B, Jones K, Wang GL, et al. (2010) Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells. Faseb J 24: 3706-3719.
37. Tian B, White RJ, Xia T, Welle S, Turner DH, et al. (2000) Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR. RNA 6: 79-87.
38. Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BR, (2003) Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 5: 834-839.
39. Puthenveetil S, Whitby L, Ren J, Kelnar K, Krebs JF, et al. (2006) Controlling activation of the RNA-dependent protein kinase by siRNAs using site-specific chemical modification. Nucleic Acids Res 34: 4900-4911.
40. Stein A, Crothers DM, (1976) Conformational changes of transfer RNA. The role of magnesium(II). Biochemistry 15: 160-168.
41. Sampson JR, Uhlenbeck OC, (1988) Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed in vitro. Proc Natl Acad Sci U S A 85: 1033-1037.
42. Nobles KN, Yarian CS, Liu G, Guenther RH, Agris PF, (2002) Highly conserved modified nucleosides influence Mg2+-dependent tRNA folding. Nucleic Acids Res 30: 4751-4760.
43. Jones CI, Spencer AC, Hsu JL, Spremulli LL, Martinis SA, et al. (2006) A counterintuitive Mg2+-dependent and modification-assisted functional folding of mitochondrial tRNAs. J Mol Biol 362: 771-786.
44. Byrne RT, Konevega AL, Rodnina MV, Antson AA, (2010) The crystal structure of unmodified tRNAPhe from Escherichia coli. Nucleic Acids Res 38: 4154-4162.
45. Yang SK, Soll DG, Crothers DM, (1972) Properties of a dimer of tRNA I Tyr 1 (Escherichia coli). Biochemistry 11: 2311-2320.
46. Madore E, Florentz C, Giege R, Lapointe J, (1999) Magnesium-dependent alternative foldings of active and inactive Escherichia coli tRNA(Glu) revealed by chemical probing. Nucleic Acids Res 27: 3583-3588.
47. Loehr JS, Keller EB, (1968) Dimers of alanine transfer RNA with acceptor activity. Proc Natl Acad Sci U S A 61: 1115-1122.
48. Wittenhagen LM, Kelley SO, (2002) Dimerization of a pathogenic human mitochondrial tRNA. Nat Struct Biol 9: 586-590.
49. Roy MD, Wittenhagen LM, Kelley SO, (2005) Structural probing of a pathogenic tRNA dimer. RNA 11: 254-260.
50. Kariko K, Buckstein M, Ni H, Weissman D, (2005) Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23: 165-175.
51. Björk G (1995) Biosynthesis and Function of Modified Nucleosides. In: Söll D, RajBhandary UL, editors. tRNA: Structure, Biosynthesis and Function. Washington, D.C.: American Society for Microbiology Press. 165-205.
52. Jeffrey IW, Kadereit S, Meurs EF, Metzger T, Bachmann M, et al. (1995) Nuclear localization of the interferon-inducible protein kinase PKR in human cells and transfected mouse cells. Exp Cell Res 218: 17-27.
53. Florentz C, Sohm B, Tryoen-Toth P, Putz J, Sissler M, (2003) Human mitochondrial tRNAs in health and disease. Cell Mol Life Sci 60: 1356-1375.
54. Björk GR, Ericson JU, Gustafsson CE, Hagervall TG, Jonsson YH, et al. (1987) Transfer RNA modification. Annu Rev Biochem 56: 263-287.
55. Hunter SE, Spremulli LL, (2004) Effects of mutagenesis of residue 221 on the properties of bacterial and mitochondrial elongation factor EF-Tu. Biochim Biophys Acta 1699: 173-182.
56. Manche L, Green SR, Schmedt C, Mathews MB, (1992) Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol Cell Biol 12: 5238-5248.
57. Zheng X, Bevilacqua PC, (2004) Activation of the protein kinase PKR by short double-stranded RNAs with single-stranded tails. RNA 10: 1934-1945.
58. Nallagatla SR, Toroney R, Bevilacqua PC, (2008) A brilliant disguise for self RNA: 5'-end and internal modifications of primary transcripts suppress elements of innate immunity. RNA Biol 5: 140-144.
59. Graham RL, Sims AC, Brockway SM, Baric RS, Denison MR, (2005) The nsp2 replicase proteins of murine hepatitis virus and severe acute respiratory syndrome coronavirus are dispensable for viral replication. J Virol 79: 13399-13411.
60. Nie Y, Hammond GL, Yang JH, (2007) Double-stranded RNA deaminase ADAR1 increases host susceptibility to virus infection. J Virol 81: 917-923.
61. Wang X, Liao Y, Yap PL, Png KJ, Tam JP, et al. (2009) Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells. J Virol 83: 12462-12472.
62. Hovanessian AG, (1993) Interferon-induced dsRNA-activated Protein Kinase (PKR): Antiproliferative, Antiviral and Antitumoral Functions. Semin Virol 4: 237-245.
63. Sohm B, Sissler M, Park H, King MP, Florentz C, (2004) Recognition of human mitochondrial tRNALeu(UUR) by its cognate leucyl-tRNA synthetase. J Mol Biol 339: 17-29.
64. Jones CN, Jones CI, Graham WD, Agris PF, Spremulli LL, (2008) A disease-causing point mutation in human mitochondrial tRNAMet rsults in tRNA misfolding leading to defects in translational initiation and elongation. J Biol Chem 283: 34445-34456.
65. Wakita K, Watanabe Y, Yokogawa T, Kumazawa Y, Nakamura S, et al. (1994) Higher-order structure of bovine mitochondrial tRNA(Phe) lacking the 'conserved' GG and T psi CG sequences as inferred by enzymatic and chemical probing. Nucleic Acids Res 22: 347-353.
66. Spencer AC, Heck A, Takeuchi N, Watanabe K, Spremulli LL, (2004) Characterization of the human mitochondrial methionyl-tRNA synthetase. Biochemistry 43: 9743-9754.
67. Gehrig S, Eberle ME, Botschen F, Rimbach K, Eberle F, et al. (2012) Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. J Exp Med 209: 225-233.