Small Circular Satellite RNAs

C H A P T E R

61 Small Circular Satellite RNAs Beatriz Navarro, Luisa Rubino and Francesco Di Serio National Research Council, Bari, Italy

INTRODUCTION The infectivity of small circular satellite RNAs (sc-satRNAs) depends on a helper virus. However, sc-satRNAs resemble viroids in several features, including the small (220
257 nt) and single-stranded genome, the accumulation in the infected host as covalently-closed circular RNAs, the replication through rolling-circle mechanisms based on RNA intermediates only, and the inability to code for proteins, with one exception. In addition, sc-satRNAs are endowed with self-cleaving (and some with self-ligation) activity mediated by ribozymes, another feature shared with some viroids, thus reinforcing the hypothesis that these two groups of subviral infectious RNAs may have a monophyletic origin (Elena et al., 2001). However, a key biological difference exists between sc-satRNAs and viroids regarding the molecular machinery needed for replication, which is supplied by the helper virus and the host in the first case, but only by the host in the second. In addition, in contrast to viroids, sc-satRNAs are encapsidated by the helper virus coat protein. This chapter focuses on the main structural and biological features of sc-satRNAs, pointing out the role of hammerhead and hairpin ribozymes in their replication. Readers looking for additional information on sc-satRNAs may check previous reviews (Bruening et al., 1991; Diener, 1991; Francki, 1987; Rao and Kalantidis, 2015; Roossinck et al., 1992; Rubino et al., 2003; Symons and Randles, 1999; Taliansky and Palukaitis, 1999).

Viroids and Satellites. DOI: http://dx.doi.org/10.1016/B978-0-12-801498-1.00061-9

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STRUCTURAL PROPERTIES sc-satRNAs share little or no sequence similarity with the helper virus and host genomes, accumulate in vivo as circular and linear forms, and do not code for proteins. The latter feature, supported by studies with several sc-satRNAs (Kiberstis and Zimmern, 1984; MorrisKrsinich and Forster, 1983; Owens and Schneider, 1977; Rubino et al., 1990), has been recently questioned for the sc-satRNA of rice yellow mottle virus (RYMV) (see below). sc-satRNAs are associated with members of the genera Sobemovirus, Nepovirus, and Polerovirus (Table 61.1). Circular and linear forms of scsatRNAs coexist in infected tissues; the circular form is encapsidated predominantly by sobemoviruses and the linear form by nepo and poleroviruses (Table 61.1). sc-satRNAs encapsidated as circular forms are also termed virusoids. Apart from the conserved nucleotides of the ribozymes (see below), only a few sequence elements are shared among sc-satRNAs. The scsatRNA associated with the lucerne transient streak virus (LTSV) and RYMV share a 50-nt region with high sequence identity (89%) located in the left terminal domain of their proposed secondary structure (Collins et al., 1998). This region includes a GAUUUU motif conserved in the same position in all sc-satRNAs (Keese et al., 1983) and is suggested to play a role in replication (Davies et al., 1990). Due to their high level of self-complementary sequences, a compact secondary structure constituted by double-stranded regions interposed between bulges and loops, has been proposed for sc-satRNAs, with some of them assuming quasi rod-like and others more branched conformations (Rubino et al., 2003). In the sc-satRNA associated with cereal yellow dwarf virus-RPV (CYDV-RPV), the proposed branched secondary structure was confirmed by in vitro probing, and structural elements that may interact with viral proteins were proposed (Song and Miller, 2004).

BIOLOGICAL PROPERTIES Replication of sc-satRNAs depends on both the helper virus and the host, although related viruses can support replication of a different scsatRNA as exemplified by some sobemoviruses (Roossinck et al., 1992). sc-satRNAs can attenuate or exacerbate the symptoms caused by their helper viruses and they can alter (usually reduce) viral RNA accumulation. In sc-satRNAs associated with nepoviruses, both situations have been reported: sc-satRNAs of tobacco ringspot virus (TRSV) and chicory

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TABLE 61.1

Small Circular Satellite RNAs (sc-satRNAs) Genus of the helper virus

Encapsidated RNA

sc-satRNA size (nt)

(1) ribozymea

(2) ribozymea

Reference

Lucerne transient streak virus

Sobemovirus

Circular

322 and 324

HH

HH

Keese et al. (1983)

Solanum nodiflorum mottle virus

Sobemovirus

Circular

377

HH




Haseloff and Symons (1982)

Subterranean clover mottle virus

Sobemovirus

Circular

332 and 328

HH




Davies et al. (1990)

Velvet tobacco mottle virus

Sobemovirus

Circular

366

HH




Haseloff and Symons (1982)

Rice yellow mottle virus

Sobemovirus

Circular

220

HH




Collins et al. (1998)

Arabis mosaic virus satellite

Nepovirus

Linear

300
301

HH

HP

Kaper and Collmer (1988)

Chicory yellow mottle virus

Nepovirus

Linear

457

HH

HP

Rubino et al. (1990)

Tobacco ringspot virus satellite

Nepovirus

Linear

359

HH

HP

Buzayan et al. (1986c)

Cereal yellow dwarf virusRPVb

Polerovirus

Linear

322

HH

HH

Miller et al. (1991)

Helper virus

a

HH, hammerhead ribozyme; HP, hairpin ribozyme. The helper virus, formerly known as the RPV serotype of the barley yellow dwarf virus (genus Luteovirus), has been reclassified as cereal yellow dwarf virus-RPV (CYDV-RPV) in the new genus Polerovirus.

b

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61. SMALL CIRCULAR SATELLITE RNAS

yellow mottle virus reduce the accumulation of their supporting viruses and attenuate the severity of the symptoms induced by the viruses alone (Kaper and Collmer, 1988; Piazzolla et al., 1986), whereas the sc-satRNA of the arabis mosaic virus has an opposite effect in Chenopodium quinoa and hop (Davies and Clark, 1983). The ability of some satellites to attenuate the symptoms induced by their helper viruses suggested that satellites may act as antiviral agents (Gerlach et al., 1987). sc-satRNAs-derived small RNAs of 21
24 nt similar to microRNAs and small interfering RNAs, the hallmarks of RNA silencing (Axtell, 2013), have been identified in plants infected by the sc-satRNA associated with CYDV-RPV and proposed to play a role in pathogenesis by downregulation of specific host mRNAs (Wang et al., 2001, 2004). This hypothesis, recently validated for a small linear satellite RNA of cucumber mosaic virus (Shimura et al., 2011; Smith et al., 2011) and a chloroplast-replicating viroid (Navarro et al., 2012), is awaiting experimental proof in sc-satRNAs. Since the replicating CYDV-RPV sc-satRNA efficiently induced de novo cytosine methylation of its homologous transgenic DNA, resembling the RNA-directed DNA methylation induced by nuclear-replicating viroids (Wassenegger et al., 1994), the possibility that sc-sRNAs could interfere with host gene expression by targeting DNA for methylation has also been suggested (Wang et al., 2001). RNA silencing could also act as a plant defense against sc-satRNAs promoting their sequence-specific degradation. The compact secondary structure may help sc-satRNAs to escape RNA silencing-mediated degradation. Moreover, viral-encoded proteins supply at least two additional barriers against RNA silencing: sc-satRNA encapsidation by viral coat protein (Wang et al., 2004) and impairment of RNA silencing by virus-encoded RNA silencing suppressor proteins.

ROLE OF SELF-CLEAVAGE IN ROLLING-CYCLE REPLICATION Studies showing that synthesis of sc-satRNA associated with velvet tobacco mottle virus is not inhibited in vivo by the low concentrations of α-amanitin that impair the activity of host DNA-dependent RNA polymerase II, indicated that, in contrast to nuclear-replicating viroids, this enzyme is not involved in sc-satRNAs replication (Wu et al., 1986). In addition, actinomycin D, which inhibits host DNA-dependent RNA synthesis, did not affect replication of TRSV sc-satRNA in protoplasts coinfected with TRSV (Buckley and Bruening, 1990), thus suggesting the

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ROLE OF SELF-CLEAVAGE IN ROLLING-CYCLE REPLICATION

663

involvement of the RNA-dependent RNA-polymerase (RNA replicase) encoded (in part) by the virus. This view was further supported by more recent studies that identified the RNA replicase as the only viral component needed for CYDV-RPV sc-satRNA replication (Song and Miller, 2004). Since helper viruses replicate in the cytoplasm associated with membranous vesicles, sc-satRNA replication likely occurs in the same subcellular compartment, although no conclusive experimental evidence has been obtained yet (Flores et al., 2011; Rao and Kalantidis, 2015). Based on the presence in infected tissues of circular and multimeric forms of sc-satRNAs and their ability to self-cleave through the ribozymes that at least one of the strands can form, a rolling-circle replication mechanism was proposed (Branch and Robertson, 1984). Similarly to viroids, symmetric and asymmetric variants were suggested depending on the presence or absence in the infected tissues of the circular RNA of minus polarity, respectively (Forster and Symons, 1987). Since sc-satRNAs lack coding capacity, the plus polarity has been arbitrarily assigned to the sc-satRNA strand that accumulates at higher level in vivo. According to the rolling-circle mechanism, the monomeric circular plus strand RNA is reiteratively transcribed to produce multimeric linear minus RNA strands that either self-cleave and ligate to form circular monomers (symmetric variant) or remain as multimers (asymmetric variant). The minus strands serve as templates for the synthesis of linear oligomeric plus strand RNAs, which are finally cleaved and circularized to generate the monomeric circular RNA progeny (Flores et al., 2011). Cleavage of oligomeric RNA intermediates is an autolytic process mediated by cis-acting ribozymes. According to the active conformation assumed, the ribozymes in sc-satRNAs are termed hammerhead or hairpin ribozymes, the self-cleavage of which generate 50 hydroxyl and 20
30 cyclic phosphodiester termini. The first evidence of self-cleavage in vitro was obtained with purified natural linear oligomers (Prody et al., 1986) or in vitro-generated transcripts (Buzayan et al., 1986a) of the sc-satRNA associated with TRSV, which resulted in infectious linear monomers. Based on the structural features characteristic of ribozymes, self-cleavage mediated by hammerhead ribozymes was predicted and experimentally shown in vitro for the plus polarity strand of all sc-satRNAs, whereas self-cleavage of the minus strand was reported only for some of them, including those associated with LTSV and CYDV-RPV (mediated by hammerhead ribozymes) and with nepoviruses (mediated by hairpin ribozymes) (Table 61.1). Self-cleaving activity in one or both polarity strands is indicative of the asymmetric or symmetric replication pathway followed by the sc-satRNA, respectively. Strong support for the ribozyme role in vivo was supplied by data showing reversion in vivo of mutations impairing the autolytic

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processing in vitro of the sc-satRNA associated with LTSV (Sheldon and Symons, 1993). After self-cleavage, an RNA ligase that circularizes the monomeric linear RNAs is needed to complete the rolling-circle replication. This catalytic activity, likely virus-independent (Chay et al., 1997), may be mediated by the same ribozyme acting in the reverse direction. Interestingly, the RNA ligase activity of the hairpin ribozyme is significantly higher than that of the hammerhead ribozyme (Fedor, 2000). In line with this view, in vitro circularization in the absence of proteins has been shown for the minus strand of TRSV sc-satRNA, which contains a hairpin ribozyme (Buzayan et al., 1986b). In contrast, low efficiency self-ligation in vitro was observed for the plus RNA of the same satellite containing a hammerhead ribozyme (Nelson et al., 2005; Prody et al, 1986). Similarly to viroids containing hammerhead ribozymes, circularization of the monomeric plus linear sc-satRNA of TRSV most likely requires a host RNA ligase (Kiberstis et al., 1985) that must colocalize with the site of sc-satRNA and helper virus replication (Flores et al., 2011). Alternative RNA foldings have been proposed to facilitate efficient ligation of linear sc-satRNA forms (Chay et al., 1997).

STRUCTURE OF THE HAMMERHEAD AND HAIRPIN RIBOZYMES OF SC-SATRNAS The minimal hammerhead ribozyme consists of three base-paired helices of variable composition and length surrounding a 15-nt core containing 11 conserved nt around the self-cleavage site (Flores et al., 2001). This site is preceded by a GUC motif in most natural hammerheads. Exceptions to this rule are the hammerheads of the minus strands of scsatRNAs associated with LTSV (Keese et al., 1983) and velvet tobacco mottle virus (Haseloff and Symons, 1982), where the triplet is GUA, and the hammerhead of the plus strand of the CYDV-RPV sc-satRNA (Miller et al., 1991), in which an AUA triplet precedes the self-cleavage site (Fig. 61.1). Another peculiarity is the presence of an extra U after the conserved GA doublet in the plus hammerheads of the sc-satRNAs associated with LTSV and arabis mosaic virus (Fig. 61.1). The scsatRNA hammerheads reported in Fig. 61.1 are presented in a Y-shaped conformation derived from crystallography studies that revealed complex noncanonical interactions between the residues forming the central core (Pley et al., 1994). Tertiary interactions outside the catalytic core, essential for in vivo self-cleavage of some viroid hammerheads (De la Pen˜a et al., 2003; Khvorova et al., 2003), were also identified in the sc-satRNA TRSV hammerhead (Chi et al., 2008). In the CYDV-RPV-associated

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STRUCTURE OF THE HAMMERHEAD AND HAIRPIN RIBOZYMES OF SC-SATRNAS

FIGURE 61.1

665

Sequence and secondary structure of the minimal ribozyme domains of sc-satRNAs. Panel A: Hammerhead structures are represented according to Y-shape. The nucleotides forming the conserved catalytic core are boxed and in bold; stems are numbered according to a previous convention (Forster and Symons, 1987). The extra U after the conserved GA in the plus strand hammerhead of sc-satRNAs associated with LTSV and ArMV is highlighted in bold. The plus strand of sc-satRNA associated with RYMV most likely self-cleaves in vivo by a double-hammerhead structure (not shown). Panel B: Minimal hairpin ribozyme structures are represented based on Fedor (2000). H1, H2, H3, and H4 indicate base-paired helices, including interacting loops (A and B). Conserved nucleotides in bold are required for activity and regions of RNA that are not involved in hairpin structure are drawn as continuous lines. In both panels, the self-cleavage site is indicated by an arrow and numbering refers to plus strands.

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61. SMALL CIRCULAR SATELLITE RNAS

sc-satRNA, a pseudoknot inhibits the hammerhead-mediated self-cleavage of the monomeric plus RNA (Miller and Silver, 1991), while self-cleavage of the multimeric RNAs of this satellite likely occurs via an alternative double-hammerhead structure, thus suggesting that a conformational switch of sc-satRNAs associated with CYDV-RPV controls ribozyme activity during replication (Song and Miller, 2004). Hairpin ribozymes have been identified only in the minus strand of the three sc-satRNAs associated with nepovirus (Fig. 61.1). The secondary structure proposed for the hairpin ribozyme (also called paperclip) contains a catalytic core that consists of four base-paired helices separated by two unpaired conserved loops (Berzal-Herranz et al., 1993). The crystal structure of the hairpin ribozyme has been resolved and showed the presence of tertiary interactions that facilitate the catalysis (Rupert and Ferre´-D’Amare´, 2001).

DO SC-SATRNAS CODE FOR FUNCTIONAL PROTEINS? Recently, AbouHaidar et al. (2014) showed that the sc-satRNA associated with RYMV, with the smallest size (220 nt) among sc-satRNAs and viroids, codes for a 16-kDa highly-basic polypeptide of unknown function that has been detected in infected tissues and in purified virions. The mechanism of translation initiation proposed for the RYMV sc-satRNA-encoded protein is unusual since it does not operate by the conventional ribosome-scanning pathway. The authors propose an alternative mechanism based on direct and reiterative (at least two rounds) translation of the circular RYMV sc-satRNA. Whether this is a situation restricted to this sc-satRNA is not known. However, extension of the coding properties to the other sc-satRNAs is unlikely because a similar coding potential seems absent in the other sc-satRNAs, and inconsistent with the insertion of one or two nucleotides observed in natural sequence variants of several sc-satRNAs (Table 61.1).

OTHER PUTATIVE SC-SATELLITE RNAS A new member of the sc-satRNA group could be a small circular RNA of 365 nt identified in mulberry trees (mulberry small circular RNAs, mscRNA) in China. This RNA was initially considered a viroid associated with mulberry mosaic dwarf disease (Wang et al., 2010). However, attempts to infect healthy mulberry seedlings with purified circular forms and in vitro transcripts of the mscRNA were

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unsuccessful, suggesting that this RNA is not a viroid. Moreover, in vitro self-cleaving hammerhead and hairpin ribozymes have been identified in the mscRNA plus and minus strands, respectively, a feature only found in sc-satRNA associated with nepoviruses. The satellite nature of mscRNA is further supported by the finding of a nepovirus in mulberry plants coinfected by mscRNA (S. Li, B. Navarro and T. Sano, unpublished data).

Acknowledgments Research in B.N., L.R., and F.D.S. laboratories has been partially funded by a dedicated grant of the Ministero dell’Economia e Finanze Italiano to the CNR (CISIA, Legge n. 191/ 2009) and by a joint project in the frame of scientific cooperation between Consiglio Nazionale delle Ricerche (Italy) and Chinese Academy of Agricultural Sciences (China) 2011
13 to B.N.

References AbouHaidar, M.G., Venkataraman, S., Golshani, A., Liu, B., Ahmad, T., 2014. Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt. Proc. Natl. Acad. Sci. USA 111, 14542
14547. Axtell, M.J., 2013. Classification and comparison of small RNAs from plants. Annu. Rev. Plant Biol. 64, 137
159. Berzal-Herranz, A., Joseph, S., Chowrira, B.M., Butcher, S.E., Burke, J.M., 1993. Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J. 12, 2567
2573. Branch, A.D., Robertson, H.D., 1984. A replication cycle for viroids and other small infectious RNAs. Science 223, 450
455. Bruening, G., Feldstein, P.A., Buzayan, J.M., van Tol, H., deBear, J., Gough, G.R., et al., 1991. Satellite tobacco ringspot virus satellite RNA: self-cleavage and ligation reactions in replication. In: Maramorosch, K. (Ed.), Viroids and Satellites: Molecular Parasites at the Frontier of Life. CRC Press, Boca Raton, FL, pp. 141
158. Buckley, B., Bruening, G., 1990. Effect of actinomycin D on replication of satellite tobacco ringspot virus RNA in plant protoplasts. Virology 177, 298
304. Buzayan, J.M., Gerlach, W.L., Bruening, G., 1986a. Non-enzymatic cleavage and ligation of RNAs complementary to a plant virus satellite RNA. Nature 323, 349
353. Buzayan, J.M., Gerlach, W.L., Bruening, G., 1986b. Satellite tobacco ringspot virus RNA: a subset of the RNA sequence is sufficient for autolytic processing. Proc. Natl. Acad. Sci. USA 83, 8859
8862. Buzayan, J.M., Gerlach, W.L., Bruening, G., Keese, P., Gould, A.R., 1986c. Nucleotide sequence of satellite tobacco ringspot virus RNA and its relationship to multimeric forms. Virology 151, 186
199. Chay, C.A., Guan, X., Bruening, G., 1997. Formation of circular satellite tobacco ringspot virus RNA in protoplasts transiently expressing the linear RNA. Virology 239, 413
425. Chi, Y.I., Martick, M., Lares, M., Kim, R., Scott, W.G., Kim, S.H., 2008. Capturing hammerhead ribozyme structures in action by modulating general base catalysis. PLoS Biol. 6, e234.

XI. TYPES OF SATELLITES

668

61. SMALL CIRCULAR SATELLITE RNAS

Collins, R.F., Gellatly, D.L., Sehgal, O.P., Abouhaidar, M.G., 1998. Self-cleaving circular RNA associated with rice yellow mottle virus is the smallest viroid-like RNA. Virology 241, 269
275. Davies, C., Haseloff, J., Symons, R.H., 1990. Structure, self-cleavage, and replication of two viroid-like satellite RNAs (virusoids) of subterranean clover mottle virus. Virology 177, 216
224. Davies, D.L., Clark, M.F., 1983. A satellite-like nucleic acid of arabis mosaic virus associated with hop nettled disease. Ann. Appl. Biol. 103, 439
448. De la Pen˜a, M., Gago, S., Flores, R., 2003. Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity. EMBO J. 22, 5561
5570. Diener, T.O., 1991. The frontiers of life: the viroids and viroid-like satellite RNAs. In: Maramorosch, K. (Ed.), Viroids and Satellites: Molecular Parasites at the Frontier of Life. CRC Press, Boca Raton, FL, pp. 1
21. Elena, S.F., Dopazo, J., Flores, R., Diener, T.O., Moya, A., 2001. Phylogenetic analysis of viroid and viroid-like satellite RNAs from plants: a reassessment. J. Mol. Evol. 53, 155
159. Fedor, M.J., 2000. Structure and function of the hairpin ribozyme. J. Mol. Biol. 297, 269
291. ´ ., Delgado, S., Gago, S., 2011. Rolling-circle Flores, R., Grubb, D., Elleuch, A., Nohales, M.A replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: variations on a theme. RNA Biol. 8, 200
206. Flores, R., Herna´ndez, C., de la Pen˜a, M., Vera, A., Daro`s, J.A., 2001. Hammerhead ribozyme structure and function in plant RNA replication. Methods Enzymol. 341, 540
552. Forster, A.C., Symons, R.H., 1987. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell 49, 211
220. Francki, R.I., 1987. Encapsidated viroidlike RNA. In: Diener, T.O. (Ed.), The Viroids. Plenum, New York, pp. 205
218. Gerlach, W.L., Llewellyn, D., Haseloff, J., 1987. Construction of a plant disease resistance gene from the satellite RNA of tobacco ringspot virus. Nature 328, 802
805. Haseloff, J., Symons, R.H., 1982. Comparative sequence and structure of viroid-like RNAs of two plant viruses. Nucleic Acids Res. 10, 3681
3691. Kaper, J.M., Collmer, C.W., 1988. Modulation of viral plant diseases by secondary RNA agents. In: Domingo, E., Holland, J.J., Alquist, P. (Eds.), RNA Genetics. CRC Press, Boca Raton, FL, pp. 171
194. Keese, P., Bruening, G., Symons, R.H., 1983. Comparative sequence and structure of circular RNAs from two isolates of lucerne transient streak virus. FEBS Lett. 159, 185
190. Khvorova, A., Lescoute, A., Westhof, E., Jayasena, S.D., 2003. Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity. Nat. Struct. Biol. 10, 708
712. Kiberstis, P.A., Haseloff, J., Zimmern, D., 1985. 2’ Phosphomonoester, 3’-5’ phosphodiester bond at a unique site in a circular viral RNA. EMBO J. 4, 817
827. Kiberstis, P.A., Zimmern, D., 1984. Translational strategy of solanum nodiflorum mottle virus RNA: synthesis of a coat protein precursor in vitro and in vivo. Nucleic Acids Res. 12, 933
943. Miller, W.A., Hercus, T., Waterhouse, P.M., Gerlach, W.L., 1991. A satellite RNA of barley yellow dwarf virus contains a novel hammerhead structure in the self-cleavage domain. Virology 183, 711
720. Miller, W.A., Silver, S.L., 1991. Alternative tertiary structure attenuates self-cleavage of the ribozyme in the satellite RNA of barley yellow dwarf virus. Nucleic Acids Res. 19, 5313
5320. Morris-Krsinich, B.A.M., Forster, R.L.S., 1983. Lucerne transient streak virus RNA and its translation in rabbit reticulocyte lysate and wheat germ extract. Virology 128, 176
185. Navarro, B., Gisel, A., Rodio, M.E., Delgado, S., Flores, R., Di Serio, F., 2012. Small RNAs containing the pathogenic determinant of a chloroplast-replicating viroid guide degradation of a host mRNA as predicted by RNA silencing. Plant J. 70, 991
1003.

XI. TYPES OF SATELLITES

REFERENCES

669

Nelson, J.A., Shepotinovskaya, I., Uhlenbeck, O.C., 2005. Hammerheads derived from sTRSV show enhanced cleavage and ligation rate constants. Biochemistry 44, 14577
14585. Owens, R.A., Schneider, I.R., 1977. Satellite of tobacco ringspot virus RNA lacks detectable mRNA activity. Virology 890, 222
224. Piazzolla, P., Vovlas, C., Rubino, L., 1986. Symptom regulation induced by chicory yellow mottle virus satellite-like RNA. J. Phytopathol. 115, 124
129. Pley, H.W., Flaherty, K.M., McKay, D.B., 1994. Three-dimensional structure of a hammerhead ribozyme. Nature 372, 68
74. Prody, G.A., Bakos, J.T., Buzayan, J.M., Schneider, I.R., Bruening, G., 1986. Autolytic processing of dimeric plant virus satellite RNA. Science 231, 1577
1580. Rao, A.L.N., Kalantidis, K., 2015. Virus-associated small satellite RNAs and viroids display similarities in their replication strategies. Virology 479-480, 627
636. Roossinck, M.J., Sleat, D., Palukaitis, P., 1992. Satellite RNAs of plant viruses: structures and biological effects. Microbiol. Rev. 56, 265
279. Rubino, L., Tousignant, M.E., Steger, G., Kaper, J.M., 1990. Nucleotide sequence and structural analysis of two satellite RNAs associated with chicory yellow mottle virus. J. Gen. Virol. 71, 1897
1903. Rubino., L., Martelli, G.P., Di Serio, F., 2003. Viroid-like satellite RNAs. In: Hadidi, A., Flores, R., Randles, J.W., Semancik, J.S. (Eds.), Viroids. CSIRO Publishing, Collingwood, VIC, pp. 76
86. Rupert, P.B., Ferre´-D’Amare´, A.R., 2001. Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410, 780
786. Sheldon, C.C., Symons, R.H., 1993. Is hammerhead self-cleavage involved in the replication of a virusoid in vivo? Virology 194, 463
474. Shimura, H., Pantaleo, V., Ishihara, T., Myojo, N., Inaba, J., Sueda, K., et al., 2011. A viral satellite RNA induces yellow symptoms on tobacco by targeting a gene involved in chlorophyll biosynthesis using the RNA silencing machinery. PLoS Pathog. 7, e1002021. Smith, N.A., Eamens, A.L., Wang, M.B., 2011. Viral small interfering RNAs target host genes to mediate disease symptoms in plants. PLoS Pathog. 7, e1002022. Song, S.I., Miller, W.A., 2004. Cis and trans requirements for rolling circle replication of a satellite RNA. J. Virol. 78, 3072
3082. Symons, R.H., Randles, J.W., 1999. Encapsidated circular viroid-like satellite RNAs (virusoids) of plants. Curr. Top. Microbiol. Immunol. 239, 81
105. Taliansky, M.E., Palukaitis, P.F., 1999. Satellite RNAs and satellite virus. In: Webster, B.G., Granoff, A. (Eds.), Encyclopedia of Virology. Academic Press, San Diego, CA, pp. 1607
1615. Wang, M.B., Bian, X.Y., Wu, L.M., Liu, L.X., Smith, N.A., Isenegger, D., et al., 2004. On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites. Proc. Natl. Acad. Sci. USA 101, 3275
3280. Wang, M.B., Wesley, S.V., Finnegan, E.J., Smith, N.A., Waterhouse, P.M., 2001. Replicating satellite RNA induces sequence-specific DNA methylation and truncated transcripts in plants. RNA. 7, 16
28. Wang, W.B., Fei, J.M., Wu, Y., Bai, X.C., Yu, F., Shi, G.F., et al., 2010. A new report of a mosaic dwarf viroid-like disease on mulberry trees in China. Pol. J. Microbiol. 59, 33
36. Wassenegger, M., Heimes, S., Riedel, L., Sa¨nger, H.L., 1994. RNA-directed de novo methylation of genomic sequences in plants. Cell 76, 567
576. Wu, J.-G., Lu, W.-J., Tien, P., 1986. Multiplication of velvet tobacco mottle virus in Nicotiana clevelandii protoplasts is resistant to α-amanitin. J. Gen. Virol. 67, 2757
2762.

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