Viroids: From genotype to phenotype just relying on RNA sequence and structural motifs

Frontiers in Microbiology

Volumn 3, Issue JUN, 2012, Pages

  Flores, Ricardo ^a   Serra, Pedro ^a   Minoia, Sofía ^a   Di Serio, Francesco ^b   Navarro, Beatriz ^b  

^a Ciudad Politécnica de la Innovación   (Spain)

^b INSTITUTE FOR SUSTAINABLE PLANT PROTECTION   (Italy)

Author keywords

Catalytic RNAs; Hammerhead ribozyme; RNA silencing; Small non coding RNAs

Indexed keywords

EID: 84872312259     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2012.00217     Document Type: Article

References (139)

1. Abraitiene, A., Zhao,Y., and Hammond, R. (2008). Nuclear targeting by fragmentation of the potato spindle tuber viroid genome. Biochem. Biophys. Res. Commun. 368, 470-475.
2. Ambrós, S., Hernández, C., Desvignes, J. C., and Flores, R. (1998). Genomic structure of three phenotypically different isolates of peach latent mosaic viroid: implications of the existence of constraints limiting the heterogeneity of viroid quasispecies. J. Virol. 72, 7397-7406.
3. Ambrós, S., Hernández, C., and Flores, R. (1999). Rapid generation of genetic heterogeneity in progenies from individual cDNA clones of peach latent mosaic viroid in its natural host. J. Gen. Virol. 80, 2239-2252.
4. Baumstark,T.,Schröder,A. R.,and Riesner, D. (1997). Viroid processing: switch from cleavage to ligation is driven by a change from a tetraloop to a loop E conformation. EMBO J. 16, 599-610.
5. Bojic, T., Beeharry, Y., Zhang, D. J., and Pelchat, M. (2012). Tomato RNA polymerase II interacts with the rod-like conformation of the left terminal domain of the potato spindle tuber viroid positive RNA genome. J. Gen. Virol. (in press). doi:10.1099/vir.0.041574-41570
6. Branch, A. D., Benenfeld, B. J., and Robertson, H. D. (1985). Ultraviolet light-induced crosslinking reveals a unique region of local tertiary structure in potato spindle tuber viroid and HeLa 5S RNA. Proc. Natl. Acad. Sci. U.S.A. 82, 6590-6594.
7. Branch, A. D., Benenfeld, B. J., and Robertson, H. D. (1988). Evidence for a single rolling circle in the replication of potato spindle tuber viroid. Proc. Natl. Acad. Sci. U.S.A. 85, 9128-9132.
8. Branch, A. D., and Robertson, H. D. (1984). A replication cycle for viroids and other small infectious RNAs. Science 223, 450-454.
9. Bussière, F., Ouellet, J., Côté, F., Lévesque, D., and Perreault, J. P. (2000). Mapping in solution shows the peach latent mosaic viroid to possess a new pseudoknot in a complex, branched secondary structure. J. Virol. 74, 2647-2654.
10. Candresse, T., Góra-Sochackab, A., and Zagórski, W. (2001). Restoration of secondary hairpin II is associated with restoration of infectivity of a non-viable recombinant viroid. Virus Res. 75, 29-34.
11. Carbonell, A., De la Peña, M., Flores, R., and Gago, S. (2006). Effects of the trinucleotide preceding the self-cleavage site on eggplant latent viroid hammerheads: differences in coand post-transcriptional selfcleavage may explain the lack of trinucleotide AUC in most natural hammerheads. Nucleic Acids Res. 34, 5613-5622.
12. Carbonell, A., Flores, R., and Gago, S. (2011). Trans-cleaving hammerhead ribozymes with tertiary stabilizing motifs: in vitro and in vivo activity against a structured viroid RNA. Nucleic Acids Res. 39, 2432-2444.
13. Carthew, R. W., and Sontheimer, E. J. (2009). Origins and mechanisms of miRNAs and siRNAs. Cell 136, 642-655.
14. Chi, Y. I., Martick, M., Lares, M., Kim, R., Scott, W. G., and Kim, S. H. (2008). Capturing hammerhead ribozyme structures in action by modulating general base catalysis. PLoS Biol. 6, e234. doi:10.1371/journal.pbio.0060234
15. Daròs, J. A., and Flores, R. (2004). Arabidopsis thaliana has the enzymatic machinery for replicating representative viroid species of the family Pospiviroidae. Proc. Natl. Acad. Sci. U.S.A. 101, 6792-6797.
16. Daròs, J. A., Marcos, J. F., Hernández, C.,and Flores,R. (1994). Replication of avocado sunblotch viroid: evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme processing. Proc. Natl. Acad. Sci. U.S.A. 91, 12813-12817.
17. Davies, J. W., Kaesberg, P., and Diener, T. O. (1974). Potato spindle tuber viroid. XII. An investigation of viroid RNA as a messenger for protein synthesis. Virology 61, 281-286.
18. De la Peña, M., and Flores, R. (2001). An extra nucleotide in the consensus catalytic core of a viroid hammerhead ribozyme: implications for the design of more efficient ribozymes. J. Biol. Chem. 276, 34586-34593.
19. De la Peña, M., and Flores, R. (2002). Chrysanthemum chlorotic mottle viroid RNA: dissection of the pathogenicity determinant and comparative fitness of symptomatic and nonsymptomatic variants. J. Mol. Biol. 321, 411-421.
20. De la Peña, M., Gago, S., and Flores, R. (2003). Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity. EMBO J. 22, 5561-5570.
21. De la Peña, M., Navarro, B., and Flores, R. (1999). Mapping the molecular determinant of pathogenicity in a hammerhead viroid: a tetraloop within the in vivo branched RNA conformation. Proc. Natl. Acad. Sci. U.S.A. 96, 9960-9965.
22. Delgado, S., Martínez de Alba, E., Hernández,C.,and Flores,R. (2005). A short double-stranded RNA motif of peach latent mosaic viroid contains the initiation and the selfcleavage sites of both polarity strands. J. Virol. 79, 12934-12943.
23. Diener, T. O. (1971). "A plant virus with properties of a free nucleic acid: potato spindle tuber viroid," in Comparative Virology, eds K. Maramorosch and E. Kurstak (New York: Academic Press), 433-478.
24. Diener, T. O. (1972). Potato spindle tuber viroid VIII. Correlation of infectivity with a UV-absorbing component and thermal denaturation properties of the RNA. Virology 50, 606-609.
25. Diener, T. O. (1986). Viroid processing: a model involving the central conserved region and hairpin I. Proc. Natl. Acad. Sci. U.S.A. 83, 58-62.
26. Diener, T. O. (2003). Discovering viroids: a personal perspective. Nat. Rev. Microbiol. 1, 75-80.
27. Diener, T. O., and Raymer, W. B. (1967). Potato spindle tuber virus: a plant virus with properties of a free nucleic acid. Science 158, 378-381.
28. Ding, B. (2009). The biology of viroidhost interactions. Annu. Rev. Phytopathol. 47, 105-131.
29. Ding, B. (2010). Viroids: selfreplicating, mobile, and fastevolving noncoding regulatory RNAs. Wiley Interdiscip. Rev. RNA 1, 362-375.
30. Dingley, A. J., Steger, G., Esters, B., Riesner, D., and Grzesiek, S. (2003). Structural characterization of the 69 nucleotide potato spindle tuber viroid left-terminal domain by NMR and thermodynamic analysis. J. Mol. Biol. 334, 751-767.
31. Dubé, A., Baumstark, T., Bisaillon, M., and Perreault, J. P. (2010). The RNA strands of the plus and minus polarities of peach latent mosaic viroid fold into different structures. RNA 16, 463-473.
32. Dubé, A., Bolduc, F., Bisaillon, M., and Perreault,J. P. (2011). Mapping studies of the peach latent mosaic viroid reveal novel structural features. Mol. Plant Pathol. 12, 688-701.
33. Dufour, D., De la Peña, M., Gago, S., Flores, R., and Gallego, J. (2009). Structure-function analysis of the ribozymes of chrysanthemum chlorotic mottle viroid: a loop-loop interaction motif conserved in most natural hammerheads. Nucleic Acids Res. 37, 368-381.
34. Eiras, M., Kitajima, E. W., Flores, R., and Daròs, J. A. (2007). Existence in vivo of the loop E motif in potato spindle tuber viroid RNA. Arch. Virol. 152, 1389-1393.
35. Eiras, M., Nohales, M. A., Kitajima, E. W.,Flores,R.,andDaròs,J.A. (2011). Ribosomal protein L5 and transcription factor IIIA from Arabidopsis thaliana bind in vitro specifically potato spindle tuber viroid RNA. Arch. Virol. 156, 529-533.
36. Fadda, Z., Daròs, J. A., Fagoaga, C., Flores, R., and Duran-Vila, N. (2003a). Eggplant latent viroid (ELVd): candidate type species for a new genus within family Avsunviroidae (hammerhead viroids). J. Virol. 77, 6528-6532.
37. Fadda, Z., Daròs, J. A., Flores, R., and Durán-Vila, N. (2003b). Identification in eggplant of a variant of citrus exocortis viroid (CEVd) with a 96 nucleotide duplication in the right terminal region of the rod-like secondary structure. Virus Res. 97, 145-149.
38. Fekih Hassen, I., Massart, S., Motard, J., Roussel, S., Parisi, O., Kummert, J., Fakhfakh, H., Marrakchi, M., Perreault, J. P., and Jijakli, M. H. (2007). Molecular features of new peach latent mosaic viroid variants suggest that recombination may have contributed to the evolution of this infectious RNA.Virology 360,50-57.
39. Flores, R., Daròs, J. A., and Hernández, C. (2000). The Avsunviroidae family: viroids with hammerhead ribozymes. Adv. Virus Res. 55, 271-323.
40. Flores, R., Di Serio, F., and Hernández, C. (1997). Viroids: the noncoding genomes. Semin. Virol. 8, 65-73.
41. Flores, R., Di Serio, F., Navarro, B., Duran-Vila, N., and Owens, R. A. (2011a)."Viroids and viroid diseases of plants," in Studies in Viral Ecology, Vol. 1, Microbial and Botanical Host Systems, ed. C. J. Hurst (Hoboken, NJ: John Wiley & Sons), 311-346.
42. Flores, R., Grubb, D., Elleuch, A., Nohales, M. A., Delgado, S., and Gago, S. (2011b). Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: variations on a theme. RNA Biol. 8, 200-206.
43. Flores, R., Gas, M. E., Molina-Serrano, D., Nohales, M. A., Carbonell, A., Gago, S., De la Peña, M., and Daròs, J. A. (2009). Viroid replication: rolling-circles, enzymes and ribozymes. Viruses 1, 317-334.
44. Flores, R., Hernández, C., De la Peña, M., Vera, A., and Daròs, J. A. (2001). Hammerhead ribozyme structure and function in plant RNA replication. Meth. Enzymol. 341, 540-552.
45. Flores, R., Hernández, C., Martínez de Alba, E., Daròs, J. A., and Di Serio, F. (2005). Viroids and viroid-host interactions. Annu. Rev. Phytopathol. 43, 117-139.
46. Flores, R., and Semancik, J. S. (1982). Properties of a cell-free system for synthesis of citrus exocortis viroid. Proc. Natl. Acad. Sci. U.S.A. 79, 6285-6288.
47. Fresco, J. R., Alberts, B. M., and Doty, P. (1960). Some molecular details of the secondary structure of ribonucleic acid. Nature 188, 98-101.
48. Gago, S., De la Peña, M., and Flores, R. (2005). A kissing-loop interaction in a hammerhead viroid RNA critical for its in vitro folding and in vivo viability. RNA 11, 1073-1083.
49. Gago, S., Elena, S. F., Flores, R., and Sanjuán, R. (2009). Extremely high variability of a hammerhead viroid. Science 323, 1308.
50. Gas, M. E., Hernández, C., Flores, R., and Daròs, J. A. (2007). Processing of nuclear viroids in vivo: an interplay between RNA conformations. PLoS Pathog. 3, e182. doi:10.1371/journal.ppat.0030182
51. Gas,M. E.,Molina-Serrano,D.,Hernández, C., Flores, R., and Daròs, J. A. (2008). Monomeric linear RNA of citrus exocortis viroid resulting from processing in vivo has 5′-phosphomonoester and 3′hydroxyl termini: implications for the ribonuclease and RNA ligase involved in replication. J. Virol. 82, 10321-10325.
52. Gast, F. U., Kempe, D., and Sänger, H. L. (1998). The dimerization domain of potato spindle tuber viroid, a possible hallmark for infectious RNA. Biochemistry 37, 14098-14107.
53. Gast, F. U., Kempe, D., Spieker, R. L., and Sänger, H. L. (1996). Secondary structure probing of potato spindle tuber viroid (PSTVd) and sequence comparison with other small pathogenic RNA replicons provides evidence for central non-canonical base-pairs, large A-rich loops, and a terminal branch. J. Mol. Biol. 262, 652-670.
54. Gómez, G., and Pallás, V. (2012). Studies on subcellular compartmentalization of plant pathogenic non coding RNAs give new insights into the intracellular RNA-traffic mechanisms. Plant Physiol. 159, 558-564.
55. Góra, A., Candresse, T., and Zagórski, W. (1994). Analysis of the population structure of three phenotypically different PSTVd isolates. Arch. Virol. 138, 233-245.
56. Gozmanova, M., Denti, M. A., Minkov, I. N., Tsagris, M., and Tabler, M. (2003). Characterization of the RNA motif responsible for the specific interaction of potato spindle tuber viroid RNA (PSTVd) and the tomato protein Virp1. Nucleic Acids Res. 31, 5534-5543.
57. Grill, L. K., and Semancik, J. S. (1978). RNA sequences complementary to citrus exocortis viroid in nucleic acid preparations from infected Gynura aurantiaca. Proc. Natl. Acad. Sci. U.S.A. 75, 896-900.
58. Gross, H. J., Domdey, H., Lossow, C., Jank, P., Raba, M., Alberty, H., and Sänger, H. L. (1978). Nucleotide sequence and secondary structure of potato spindle tuber viroid. Nature 273, 203-208.
59. Gross, H. J., Krupp, G., Domdey, H., Raba, M., Jank, P., Lossow, C., Alberty, H., Ramm, K., and Sanger, H. L. (1982). Nucleotide sequence and secondary structure of citrus exocortis and chrysanthemum stunt viroid. Eur. J. Biochem. 121, 249-257.
60. Gutell, R. R., Larsen, N., and Woese, C. R. (1994). Lessons from an evolving rRNA: 16S and 23S rRNA structures from a comparative perspective. Microbiol. Rev. 58, 10-26.
61. Hadidi, A., Flores, R., Randles, J. W., and Semancik, J. S. (2003). Viroids. Collingwood: CSIRO Publishing.
62. Haseloff, J., Mohamed, N. A., and Symons, R. H. (1982). Viroid RNAs of the cadang-cadang disease of coconuts. Nature 229, 316-321.
63. Haseloff, J., and Symons, R. H. (1981). Chrysanthemum stunt viroid: primary sequence and secondary structure. Nucleic Acids Res. 9,2741-2752.
64. Henco, K., Sänger, H. L., and Riesner, D. (1979). Fine structure melting of viroids as studied by kinetic methods. Nucleic Acids Res. 6, 3041-3059.
65. Hernández, C., Di Serio, F., Ambrós, S., Daròs, J. A., and Flores, R. (2006). An element of the tertiary structure of peach latent mosaic viroid RNA revealed by UV irradiation. J. Virol. 80, 9336-9340.
66. Hernández, C., Elena, S. F., Moya, A., and Flores, R. (1992). Pear blister canker viroid is a member of the apple scar skin viroid subgroup (apscaviroids) and also has sequence homologies with viroids from other subgroups. J. Gen. Virol. 73, 2503-2507.
67. Hernández, C., and Flores, R. (1992). Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via hammerhead structures. Proc. Natl. Acad. Sci. U.S.A. 89, 3711-3715.
68. Hutchins, C., Rathjen, P. D., Forster, A. C., and Symons, R. H. (1986). Self-cleavage of plus and minus RNA transcripts of avocado sunblotch viroid. Nucleic Acids Res. 14, 3627-3640.
69. Keese, P., and Symons, R. H. (1985). Domains in viroids: evidence of intermolecular RNA rearrangements and their contribution to viroid evolution. Proc. Natl. Acad. Sci. U.S.A. 82, 4582-4586.
70. Khvorova, A., Lescoute, A., Westhof, E., and Jayasena, S. D. (2003). Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity. Nat. Struct. Biol. 10, 708-712.
71. Kolonko, N., Bannach, O., Aschermann, K., Hu, K. H., Moors, M, Schmitz, M., Steger, G., and Riesner, D. (2006). Transcription of potato spindle tuber viroid by RNA polymerase II starts in the left terminal loop. Virology 347, 392-404.
72. Koltunow, A. M., and Rezaian, M. A. (1988). Grapevine yellow speckle viroid structural features of a new viroid group. Nucleic Acids Res. 16, 849-864.
73. Koltunow, A. M., and Rezaian, M. A. (1989). Grapevine viroid-1B, a new member of the apple scar skin viroid group contains the left terminal region of tomato planta macho viroid. Virology 170, 575-578.
74. Leontis, N. B., Stombaugh, J., and Westhof, E. (2002). Motif prediction in ribosomal RNAs: lessons and prospects for automated motif prediction in homologous RNA molecules. Biochimie 84, 961-973.
75. Leontis, N. B., and Westhof, E. (2001). Geometric nomenclature and classification of RNA base pairs. RNA 7, 499-512.
76. Llave, C. (2010). Virus-derived small interferingRNAsatthecoreof plantvirus interactions. Trends Plant Sci. 15, 701-707.
77. Loss, P., Schmitz, M., Steger, G., and Riesner, D. (1991). Formation of a thermodynamically metastable structure containing hairpin II is critical for infectivity of potato spindle tuber viroid RNA. EMBO J. 10, 719-727.
78. MacRae, I. J., and Doudna, J. A. (2007). Ribonuclease revisited: structural insights into ribonuclease III family enzymes. Curr. Opin. Struct. Biol. 17, 1-8.
79. Malfitano, M., Di Serio, F., Covelli, L., Ragozzino, A., Hernández, C., and Flores, R. (2003). Peach latent mosaic viroid variants inducing peach calico contain a characteristic insertion that is responsible for this symptomatology. Virology 313, 492-501.
80. Maniataki, E., Tabler, M., and Tsagris, M. (2003). Viroid RNA systemic spread may depend on the interaction of a 71-nucleotide bulged hairpin with the host proteinVirP1. RNA 9, 346-354.
81. Martick, M., and Scott, W. G. (2006). Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell 126, 309-320.
82. Martínez, F., Marqués, J., Salvador, M. L., and Daròs, J. A. (2009). Mutational analysis of eggplant latent viroid RNA processing in Chlamydomonas reinhardtii chloroplast. J. Gen. Virol. 90, 3057-3065.
83. Mathews, D. H., and Turner, D. H. (2006). Prediction of RNA secondary structure by free energy minimization. Curr. Opin. Struct. Biol. 16, 270-278.
84. McClements, W. L., and Kaesberg, P. (1977). Size and secondary structure of potato spindle tuber viroid. Virology 76, 477-484.
85. McInnes, J. L., and Symons, R. H. (1991). "Comparative structure of viroids and their rapid detection using radioactive and nonradioactive nucleic acid probes," in Viroids and Satellites: Molecular Parasites at the Frontier of Life, ed. K. Maramorosch (Boca Raton,FL: CRC Press), 21-58.
86. Merino, E. J., Wilkinson, K. A., Coughlan, J. L., and Weeks, K. M. (2005). RNA structure analysis at single nucleotide resolution by selective 2′-hydroxyl acylation and primer extension (SHAPE). J. Am. Chem. Soc. 127, 4223-4231.
87. Motard, J., Bolduc, F., Thompson, D., and Perreault, J. P. (2008). The peach latent mosaic viroid replication initiation site is located at a universal position that appears to be defined by a conserved sequence. Virology 373, 362-375.
88. Mühlbach, H. P., and Sänger, H. L. (1979). Viroid replication is inhibited by α-amanitin. Nature 278, 185-188.
89. Navarro, B., and Flores, R. (1997). Chrysanthemum chlorotic mottle viroid: unusual structural properties of a subgroup of viroids with hammerhead ribozymes. Proc. Natl. Acad. Sci. U.S.A. 94, 11262-11267.
90. Navarro, B., Gisel, A., Rodio, M. E., Degado, S., Flores, R., and Di Serio, F. (2012a). Small RNAs containing the pathogenic determinant of a chloroplast-replicating viroid guide the degradation of a host mRNA as predicted by RNA silencing. Plant J. (in press). doi:10.1111/j.13652313X.2012.04940.x
91. Navarro, B., Gisel, A., Rodio, M. E., Degado,S.,Flores,R.,and Di Serio,F. (2012b).Viroids: how to infect a host and cause disease without encoding proteins. Biochimie 94, 1474-1480.
92. Navarro, J. A., and Flores, R. (2000). Characterization of the initiation sites of both polarity strands of a viroid RNA reveals a motif conserved in sequence and structure. EMBO J. 19, 2662-2670.
93. Navarro, J. A., Vera, A., and Flores, R. (2000). A chloroplastic RNA polymerase resistant to tagetitoxin is involved in replication of avocado sunblotch viroid. Virology 268, 218-225.
94. Nohales, M. A., Molina-Serrano, D., Flores, R., and Daròs, J. A. (2012). Involvement of the chloroplastic isoform of tRNA ligase in the replication of the viroids belonging to the family Avsunviroidae. J. Virol. doi: 10.1128/JVI.00629-12. [Epub ahead of print].
95. Nussinov,R.,and Jacobson,A. B. (1980). Fast algorithm for predicting the secondary structure of single-stranded RNA. Proc. Natl. Acad. Sci. U.S.A. 77, 6309-6313.
96. Owens, R. A., and Hammond, R. W. (2009). Viroid pathogenicity: one process, many faces. Viruses 1, 298-316.
97. Owens, R. A., Sano, T., Feldstein, P. A., Hu, Y., and Steger, G. (2003). Identification of a novel structural interaction in columnea latent viroid. Virology 313, 604-614.
98. Owens, R. A., Steger, G., Hu, Y., Fels, A., Hammond, R. W., and Riesner, D. (1996). RNA structural features responsible for potato spindle tuber viroid pathogenicity. Virology 222, 144-158.
99. Paillart, J. C., Shehu-Xhilaga, M., Marquet, R., and Mak, J. (2004). Dimerization of retroviral RNA genomes: an inseparable pair. Nat. Rev. Microbiol. 2, 461-472.
100. Papaefthimiou, I., Hamilton, A. J., Denti, M. A., Baulcombe, D. C., Tsagris, M., and Tabler, M. (2001). Replicating potato spindle tuber viroid RNA is accompanied by short RNA fragments that are characteristic of post-transcriptional gene silencing. Nucleic Acids Res. 29, 2395-2400.
101. Pelchat, M., Levesque, D., Ouellet, J., Laurendeau, S., Levesque, S., Lehoux, J., Thompson, D. A., Eastwell, K. C., Skrzeczkowski, L. J., and Perreault, J. P. (2000). Sequencing of peach latent mosaic viroid variants from nine North American peach cultivars shows that this RNA folds into a complex secondary structure. Virology 271, 37-45.
102. Polivka, H., Staub, U., and Gross, H. J. (1996). Variation of viroid profiles in individual grapevine plants: novel grapevine, yellow speckle viroid 1 mutants show alterations of hairpin I. J. Gen. Virol. 77, 155-161.
103. Prody, G. A., Bakos, J. T., Buzayan, J. M., Schneider, I. R., and Bruening, G. (1986). Autolytic processing of dimeric plant virus satellite RNA. Science 231, 1577-1580.
104. Puchta, H., Ramm, K., and Sänger, H. L. (1988). The molecular structure of hop latent viroid (HLV), a new viroid occurring worldwide in hops. Nucleic Acids Res. 16, 4197-4216.
105. Qi,Y., and Ding, B. (2003). Inhibition of cell growth and shoot development by a specific nucleotide sequence in a noncoding viroid RNA. Plant Cell 15, 1360-1374.
106. Qi, Y., Pélissier, T., Itaya, A., Hunt, E., Wassenegger, M., and Ding, B. (2004). Direct role of a viroid RNA motif in mediating directional RNA trafficking across a specific cellular boundary. Plant Cell 16, 1741-1752.
107. Qu, F., Heinrich, C., Loss, P., Steger, G., Tien, P., and Riesner, D. (1995). Multiple pathways of reversion in viroids for conservation of structural domains. EMBO J. 12, 2129-2139.
108. Riesner, D. (1991). Viroids: from thermodynamics to cellular structure and function. Mol. Plant Microbe Interact. 4, 122-131.
109. Riesner,D.,Henco,K.,Rokohl,U.,Klotz, G., Kleinschmidt,A. K., Domdey,H., Jank,P.,Gross,H. J.,and Sänger,H. L. (1979). Structure and structure formation of viroids. J. Mol. Biol. 133, 85-115.
110. Rodio, M. E., Delgado, S., De Stradis, A. E., Gómez, M. D., Flores, R., and Di Serio, F. (2007). A viroid RNA with a specific structural motif inhibits chloroplast development. Plant Cell 19, 3610-3626.
111. Rodio, M. E., Delgado, S., Flores, R., and Di Serio, F. (2006). Variants of peach latent mosaic viroid inducing peach calico: uneven distribution in infected plants and requirements of the insertion containing the pathogenicity determinant. J. Gen. Virol. 87, 231-240.
112. Sänger, H. L., Klotz, G., Riesner, D., Gross, H. J., and Kleinschmidt, A. (1976). Viroids are singlestranded covalently-closed circular RNA molecules existing as highly base-paired rod-like structures. Proc. Natl. Acad. Sci. U.S.A. 73, 3852-3856.
113. Sano, T., Candresse, T., Hammond, R. W., Diener, T. O., and Owens, R. A. (1992). Identification of multiple structural domains regulating viroid pathogenicity. Proc. Natl. Acad. Sci. U.S.A. 89, 10104-10108.
114. Schindler, I. M., and Mühlbach, H. P. (1992). Involvement of nuclear DNA-dependent RNA polymerases in potato spindle tuber viroid replication: a reevaluation. Plant Sci. 84, 221-229.
115. Schmitz,A.,and Riesner,D. (1998). Correlation between bending of the VM region and pathogenicity of different potato spindle tuber viroid strains. RNA 4, 1295-1303.
116. Schroder, A. R. W., and Riesner, D. (2002). Detection and analysis of hairpin II, an essential metastable structural element in viroid replication intermediates. Nucleic Acids Res. 30, 3349-3359.
117. Semancik, J. S., Conejero, V., and Gerhart, J. (1977). Citrus exocortis viroid: survey of protein synthesis in Xenopus laevis oocytes following addition of viroid RNA. Virology 80, 218-221.
118. Semancik, J. S., Szychowski, J. A., Rakowski, A. G., and Symons, R. H. (1994). A stable 463 nucleotide variant of citrus exocortis viroid produced by terminal repeats. J. Gen. Virol. 75, 727-732.
119. Sogo, J. M., Koller, T., and Diener, T. O. (1973). Potato spindle tuber viroid X. Visualization and size determination by electron microscopy. Virology 55, 70-80.
120. Symons, R. H. (1981). Avocado sunblotch viroid: primary sequence and proposed secondary structure. Nucleic Acids Res. 9, 6527-6537.
121. Takeda, R., and Ding, B. (2009). Viroid intercellular trafficking: RNA motifs, cellular factors and broad impacts. Viruses 1, 210-221.
122. Takeda, R., Petrov, A. I., Leontis, N. B., and Ding, B. (2011). A three-dimensional RNA motif in potato spindle tuber viroid mediates trafficking from palisade mesophyll to spongy mesophyll in Nicotiana benthamiana. Plant Cell 23, 258-272.
123. Taylor, J., and Pelchat, M. (2010). Origin of hepatitis delta virus. Future Microbiol. 5, 393-402.
124. Tsagris, E. M., Martínez de Alba, A. E., Gozmanova, M., and Kalantidis, K. (2008). Viroids. Cell. Microbiol. 10, 2168-2179.
125. Visvader, J. E., Forster, A. C., and Symons, R. H. (1985). Infectivity and in vitro mutagenesis of monomeric cDNA clones of citrus exocortis viroid indicates the site of processing of viroid precursors. Nucleic Acids Res. 13, 5843-5856.
126. Wang, M. B., Bian, X. Y., Wu, L. M., Liu, L. X., Smith, N. A., Isenegger, D.,Wu, R. M., Masuta, C., Vance, V. B., Watson, J. M., Rezaian, A., Dennis, E. S., and Waterhouse, P. M. (2004). On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites. Proc. Natl. Acad. Sci. U.S.A. 101, 3275-3280.
127. Wang,Y., Zhong, X., Itaya, A., and Ding, B. (2007). Evidence for the existence of the loop E motif of potato spindle tuber viroid in vivo. J. Virol. 81, 2074-2077.
128. Wassenegger, M., Heimes, S., and Sänger, H. L. (1994). An infectious viroid RNA replicon evolved from an in vitro-generated non-infectious viroid deletion mutant via a complementary deletion in vivo. EMBO J. 13, 6172-6177.
129. Wassenegger, M., Spieker, R. L., Thalmeir, S., Gast, F. U., Riedel, L., and Sänger, H. L. (1996). A single nucleotide substitution converts potato spindle tuber viroid (PSTVd) from a noninfectious to an infectious RNA for Nicotiana tabacum. Virology 226, 191-197.
130. Weeks, K. M., and Mauger, D. M. (2011). Exploring RNA structural codes with SHAPE chemistry. Acc. Chem. Res. 44, 1280-1291.
131. Woo,Y.-M.,Itaya,A.,Owens,R.A.,Tang, L., Hammond, R. W., Chou, H.-C., Lai, M. M. C., and Ding, B. (1999). Characterization of nuclear import of potato spindle tuber viroid RNA in permeabilized protoplasts. Plant J. 17, 627-635.
132. Wu, Q., Wang, Y., Cao, M., Pantaleo, V., Burgyan, J., Lib, W. X., and Ding, S. W. (2012). Homology-independent discovery of replicating pathogenic circular RNAs by deep sequencing and a new computational algorithm. Proc. Natl. Acad. Sci. U.S.A. 109, 3938-3943.
133. Xu, W., Bolduc, F., Hong, N., and Perreault, J. P. (2012). The use of a combination of computer-assisted structure prediction and SHAPE probing to elucidate the secondary structures of five viroids. Mol. Plant Pathol. (in press). doi:10.1111/j.1364-3703.2011.00776.x
134. Yazarlou, A., Jafarpour, B., Tarighi, S., Habili, N., and Randles, J. W. (2012). New Iranian and Australian peach latent mosaic viroid variants and evidence for rapid sequence evolution. Arch. Virol. 157, 343-347.
135. Zhao, Y., Owens, R. A., and Hammond, R. W. (2001). Use of a vector based on potato virus X in a whole plant assay to demonstrate nuclear targeting of potato spindle tuber viroid. J. Gen. Virol. 82, 1491-1497.
136. Zhong, X., Archual, A. J., Amin, A. A., and Ding, B. (2008). A genomic map of viroid RNA motifs critical for replication and systemic trafficking. Plant Cell 20, 35-47.
137. Zhong, X., Leontis, N., Qiang, S., Itaya, A., Qi, Y., Boris-Lawrie, K., and Ding, B. (2006). Tertiary structural and functional analysis of a viroid RNA motif by isostericity matrix and mutagenesis reveal its essential role in replication. J. Virol. 80, 8566-8581.
138. Zhong, X., Tao, X., Stombaugh, J., Leontis, N., and Ding, B. (2007). Tertiary structure and function of an RNA motif required for plant vascular entry to initiate systemic trafficking. EMBO J. 26, 3836-3846.
139. Zuker, M., and Stiegler, P. (1981). Optimal computer folding of lare RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 9, 133-148.