RNA-directed DNA Methylation
Autoři:
Robert M. Erdmann aff001; Colette L. Picard aff002
Působiště autorů:
Center for Learning Innovation, University of Minnesota Rochester, Rochester, Minnesota, United States of America
aff001; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California, United States of America
aff002
Vyšlo v časopise:
RNA-directed DNA Methylation. PLoS Genet 16(10): e1009034. doi:10.1371/journal.pgen.1009034
Kategorie:
Topic Page
doi:
https://doi.org/10.1371/journal.pgen.1009034
Souhrn
RNA-directed DNA methylation (RdDM) is a biological process in which non-coding RNA molecules direct the addition of DNA methylation to specific DNA sequences. The RdDM pathway is unique to plants, although other mechanisms of RNA-directed chromatin modification have also been described in fungi and animals. To date, the RdDM pathway is best characterized within angiosperms (flowering plants), and particularly within the model plant Arabidopsis thaliana. However, conserved RdDM pathway components and associated small RNAs (sRNAs) have also been found in other groups of plants, such as gymnosperms and ferns. The RdDM pathway closely resembles other sRNA pathways, particularly the highly conserved RNAi pathway found in fungi, plants, and animals. Both the RdDM and RNAi pathways produce sRNAs and involve conserved Argonaute, Dicer and RNA-dependent RNA polymerase proteins.
RdDM has been implicated in a number of regulatory processes in plants. The DNA methylation added by RdDM is generally associated with transcriptional repression of the genetic sequences targeted by the pathway. Since DNA methylation patterns in plants are heritable, these changes can often be stably transmitted to progeny. As a result, one prominent role of RdDM is the stable, transgenerational suppression of transposable element (TE) activity. RdDM has also been linked to pathogen defense, abiotic stress responses, and the regulation of several key developmental transitions. Although the RdDM pathway has a number of important functions, RdDM-defective mutants in Arabidopsis thaliana are viable and can reproduce, which has enabled detailed genetic studies of the pathway. However, RdDM mutants can have a range of defects in different plant species, including lethality, altered reproductive phenotypes, TE upregulation and genome instability, and increased pathogen sensitivity. Overall, RdDM is an important pathway in plants that regulates a number of processes by establishing and reinforcing specific DNA methylation patterns, which can lead to transgenerational epigenetic effects on gene expression and phenotype.
Klíčová slova:
Arabidopsis thaliana – DNA methylation – Double stranded RNA – Flowering plants – Genetic loci – Heterochromatin – Chromatin – RNA polymerase
Zdroje
1. Dubin MJ, Mittelsten Scheid O, Becker C. Transposons: a blessing curse. Curr. Opin. Plant Biol. 2018;42:23–29. doi: 10.1016/j.pbi.2018.01.003 29453028
2. Wicker T, Gundlach H, Spannagl M, Uauy C, Borrill P, Ramírez-González RH, et al. Impact of transposable elements on genome structure and evolution in bread wheat. Genome Biol. 2018;19:103. doi: 10.1186/s13059-018-1479-0 30115100
3. Sigman MJ, Slotkin RK. The First Rule of Plant Transposable Element Silencing: Location, Location, Location. Plant Cell. 2016;28:304–13. doi: 10.1105/tpc.15.00869 26869697
4. Deniz Ö, Frost JM, Branco MR. Regulation of transposable elements by DNA modifications. Nat. Rev. Genet. 2019;20:417–431. doi: 10.1038/s41576-019-0106-6 30867571
5. Zemach A, Kim MY, Hsieh PH, Coleman-Derr D, Eshed-Williams L, Thao K, et al. The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell. 2013;153:193–205. doi: 10.1016/j.cell.2013.02.033 23540698
6. Chan SW, Zilberman D, Xie Z, Johansen LK, Carrington JC, Jacobsen SE. RNA silencing genes control de novo DNA methylation. Science. 2004;303:1336. doi: 10.1126/science.1095989 14988555
7. Pérez-Hormaeche J, Potet F, Beauclair L, Le Masson I, Courtial B, Bouché N, et al. Invasion of the Arabidopsis genome by the tobacco retrotransposon Tnt1 is controlled by reversible transcriptional gene silencing. Plant Physiol. 2008;147:1264–78. doi: 10.1104/pp.108.117846 18467467
8. Nuthikattu S, McCue AD, Panda K, Fultz D, DeFraia C, Thomas EN, et al. The initiation of epigenetic silencing of active transposable elements is triggered by RDR6 and 21–22 nucleotide small interfering RNAs. Plant Physiol. 2013;162:116–31. doi: 10.1104/pp.113.216481 23542151
9. Marí-Ordóñez A, Marchais A, Etcheverry M, Martin A, Colot V, Voinnet O. Reconstructing de novo silencing of an active plant retrotransposon. Nat. Genet. 2013;45:1029–39. doi: 10.1038/ng.2703 23852169
10. McCue AD, Panda K, Nuthikattu S, Choudury SG, Thomas EN, Slotkin RK. ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation. EMBO J. 2015;34:20–35. doi: 10.15252/embj.201489499 25388951
11. Harris CJ, Scheibe M, Wongpalee SP, Liu W, Cornett EM, Vaughan RM, et al. A DNA methylation reader complex that enhances gene transcription. Science. 2018;362:1182–1186. doi: 10.1126/science.aar7854 30523112
12. Williams BP, Pignatta D, Henikoff S, Gehring M. Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat. PLoS Genet. 2015;11:e1005142. doi: 10.1371/journal.pgen.1005142 25826366
13. Lei M, Zhang H, Julian R, Tang K, Xie S, Zhu JK. Regulatory link between DNA methylation and active demethylation in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 2015;112:3553–7. doi: 10.1073/pnas.1502279112 25733903
14. Penterman J, Zilberman D, Huh JH, Ballinger T, Henikoff S, Fischer RL. DNA demethylation in the Arabidopsis genome. Proc. Natl. Acad. Sci. U.S.A. 2007;104:6752–7. doi: 10.1073/pnas.0701861104 17409185
15. Cho J. Transposon-Derived Non-coding RNAs and Their Function in Plants. Front Plant Sci. 2018;9:600. doi: 10.3389/fpls.2018.00600 29774045
16. Mirouze M, Reinders J, Bucher E, Nishimura T, Schneeberger K, Ossowski S, et al. Selective epigenetic control of retrotransposition in Arabidopsis. Nature. 2009;461:427–30. doi: 10.1038/nature08328 19734882
17. Ito H, Gaubert H, Bucher E, Mirouze M, Vaillant I, Paszkowski J. An siRNA pathway prevents transgenerational retrotransposition in plants subjected to stress. Nature. 2011;472:115–9. doi: 10.1038/nature09861 21399627
18. Cavrak VV, Lettner N, Jamge S, Kosarewicz A, Bayer LM, Mittelsten Scheid O. How a retrotransposon exploits the plant's heat stress response for its activation. PLoS Genet. 2014;10:e1004115. doi: 10.1371/journal.pgen.1004115 24497839
19. Soppe WJ, Jacobsen SE, Alonso-Blanco C, Jackson JP, Kakutani T, Koornneef M, et al. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol. Cell. 2000;6:791–802. doi: 10.1016/s1097-2765(05)00090-0 11090618
20. Kinoshita Y, Saze H, Kinoshita T, Miura A, Soppe WJ, Koornneef M, et al. Control of FWA gene silencing in Arabidopsis thaliana by SINE-related direct repeats. Plant J. 2007;49:38–45. doi: 10.1111/j.1365-313X.2006.02936.x 17144899
21. Gouil Q, Baulcombe DC. DNA Methylation Signatures of the Plant Chromomethyltransferases. PLoS Genet. 2016;12:e1006526. doi: 10.1371/journal.pgen.1006526 27997534
22. Grover JW, Kendall T, Baten A, Burgess D, Freeling M, King GJ, et al. Maternal components of RNA-directed DNA methylation are required for seed development in Brassica rapa. Plant J. 2018;94:575–582. doi: 10.1111/tpj.13910 29569777
23. Wang G, Köhler C. Epigenetic processes in flowering plant reproduction. J. Exp. Bot. 2017;68:797–807. doi: 10.1093/jxb/erw486 28062591
24. Martinez G, Köhler C. Role of small RNAs in epigenetic reprogramming during plant sexual reproduction. Curr. Opin. Plant Biol. 2017;36:22–28. doi: 10.1016/j.pbi.2016.12.006 28088028
25. Olmedo-Monfil V, Durán-Figueroa N, Arteaga-Vázquez M, Demesa-Arévalo E, Autran D, Grimanelli D, et al. Control of female gamete formation by a small RNA pathway in Arabidopsis. Nature. 2010;464:628–32. doi: 10.1038/nature08828 20208518
26. Slotkin RK, Vaughn M, Borges F, Tanurdzić M, Becker JD, Feijó JA, et al. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell. 2009;136:461–72. doi: 10.1016/j.cell.2008.12.038 19203581
27. Martínez G, Panda K, Köhler C, Slotkin RK. Silencing in sperm cells is directed by RNA movement from the surrounding nurse cell. Nat Plants. 2016;2:16030. doi: 10.1038/nplants.2016.30 27249563
28. Erdmann RM, Hoffmann A, Walter HK, Wagenknecht HA, Groß-Hardt R, Gehring M. Molecular movement in the Arabidopsis thaliana female gametophyte. Plant Reprod, 2017;30:141–146. doi: 10.1007/s00497-017-0304-3 28695277
29. Siomi MC, Sato K, Pezic D, Aravin AA. PIWI-interacting small RNAs: the vanguard of genome defence. Nat. Rev. Mol. Cell Biol. 2011;12:246–58. doi: 10.1038/nrm3089 21427766
30. Ernst C, Odom DT, Kutter C. The emergence of piRNAs against transposon invasion to preserve mammalian genome integrity. Nat Commun. 2017;8:1411. doi: 10.1038/s41467-017-01049-7 29127279
31. Kawakatsu T, Stuart T, Valdes M, Breakfield N, Schmitz RJ, Nery JR, et al. Unique cell-type-specific patterns of DNA methylation in the root meristem. Nat Plants. 2016;2:16058. doi: 10.1038/nplants.2016.58 27243651
32. Vu TM, Nakamura M, Calarco JP, Susaki D, Lim PQ, Kinoshita T, et al. RNA-directed DNA methylation regulates parental genomic imprinting at several loci in Arabidopsis. Development. 2013;140:2953–60. doi: 10.1242/dev.092981 23760956
33. Waters AJ, Bilinski P, Eichten SR, Vaughn MW, Ross-Ibarra J, Gehring M, et al. Comprehensive analysis of imprinted genes in maize reveals allelic variation for imprinting and limited conservation with other species. Proc. Natl. Acad. Sci. U.S.A. 2013;110:19639–44. doi: 10.1073/pnas.1309182110 24218619
34. Pignatta D, Erdmann RM, Scheer E, Picard CL, Bell GW, Gehring M. Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprinting. Elife. 2014;3:e03198. doi: 10.7554/eLife.03198 24994762
35. Klosinska M, Picard CL, Gehring M. Conserved imprinting associated with unique epigenetic signatures in the Arabidopsis genus. Nat Plants. 2016;2:16145. doi: 10.1038/nplants.2016.145 27643534
36. Hatorangan MR, Laenen B, Steige KA, Slotte T, Köhler C. Rapid Evolution of Genomic Imprinting in Two Species of the Brassicaceae. Plant Cell. 2016;28:1815–27. doi: 10.1105/tpc.16.00304 27465027
37. Erdmann RM, Satyaki PRV, Klosinska M, Gehring M. A Small RNA Pathway Mediates Allelic Dosage in Endosperm. Cell Rep. 2017;21:3364–3372. doi: 10.1016/j.celrep.2017.11.078 29262317
38. Satyaki PRV, Gehring M. Paternally Acting Canonical RNA-Directed DNA Methylation Pathway Genes Sensitize Arabidopsis Endosperm to Paternal Genome Dosage. Plant Cell. 2019;31:1563–1578. doi: 10.1105/tpc.19.00047 31064867
39. Iwasaki M, Hyvärinen L, Piskurewicz U, Lopez-Molina L. Non-canonical RNA-directed DNA methylation participates in maternal and environmental control of seed dormancy. Elife. 2019;8:e37434. doi: 10.7554/eLife.37434 30910007
40. Cheng J, Niu Q, Zhang B, Chen K, Yang R, Zhu JK, et al. Downregulation of RdDM during strawberry fruit ripening. Genome Biol. 2018;19:212. doi: 10.1186/s13059-018-1587-x 30514401
41. Guo X, Ma Z, Zhang Z, Cheng L, Zhang X, Li T. Small RNA-Sequencing Links Physiological Changes and RdDM Process to Vegetative-to-Floral Transition in Apple. Front Plant Sci. 2017;8:873. doi: 10.3389/fpls.2017.00873 28611800
42. Fortes AM, Gallusci P. Plant Stress Responses and Phenotypic Plasticity in the Epigenomics Era: Perspectives on the Grapevine Scenario, a Model for Perennial Crop Plants. Front Plant Sci. 2017;8:82. doi: 10.3389/fpls.2017.00082 28220131
43. Kumar A, Bennetzen JL. Plant retrotransposons. Annu. Rev. Genet. 1999;33:479–532. doi: 10.1146/annurev.genet.33.1.479 10690416
44. Ito H, Kim JM, Matsunaga W, Saze H, Matsui A, Endo TA, et al. A Stress-Activated Transposon in Arabidopsis Induces Transgenerational Abscisic Acid Insensitivity. Sci Rep. 2016;6:23181. doi: 10.1038/srep23181 26976262
45. Liu J, Feng L, Li J, He Z. Genetic and epigenetic control of plant heat responses. Front Plant Sci. 2015;6:267. doi: 10.3389/fpls.2015.00267 25964789
46. Popova OV, Dinh HQ, Aufsatz W, Jonak C. The RdDM pathway is required for basal heat tolerance in Arabidopsis. Mol Plant. 2013;6:396–410. doi: 10.1093/mp/sst023 23376771
47. Tricker PJ, Gibbings JG, Rodríguez López CM, Hadley P, Wilkinson MJ. Low relative humidity triggers RNA-directed de novo DNA methylation and suppression of genes controlling stomatal development. J. Exp. Bot. 2012;63:3799–813. doi: 10.1093/jxb/ers076 22442411
48. Xu R, Wang Y, Zheng H, Lu W, Wu C, Huang J, et al. Salt-induced transcription factor MYB74 is regulated by the RNA-directed DNA methylation pathway in Arabidopsis. J. Exp. Bot. 2015;66:5997–6008. doi: 10.1093/jxb/erv312 26139822
49. Wassenegger M, Heimes S, Riedel L, Sänger HL. RNA-directed de novo methylation of genomic sequences in plants. Cell. 1994;76:567–76. doi: 10.1016/0092-8674(94)90119-8 8313476
50. Huang J, Yang M, Zhang X. The function of small RNAs in plant biotic stress response. J Integr Plant Biol. 2016;58:312–27. doi: 10.1111/jipb.12463 26748943
51. Raja P, Jackel JN, Li S, Heard IM, Bisaro DM. Arabidopsis double-stranded RNA binding protein DRB3 participates in methylation-mediated defense against geminiviruses. J. Virol. 2014;88:2611–22. doi: 10.1128/JVI.02305-13 24352449
52. Jackel JN, Storer JM, Coursey T, Bisaro DM. Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin. J. Virol. 2016;90:7529–7540. doi: 10.1128/JVI.00656-16 27279611
53. Diezma-Navas L, Pérez-González A, Artaza H, Alonso L, Caro E, Llave C, et al. Crosstalk between epigenetic silencing and infection by tobacco rattle virus in Arabidopsis. Mol. Plant Pathol. 2019;20:1439–1452. doi: 10.1111/mpp.12850 31274236
54. Calil IP, Fontes EPB. Plant immunity against viruses: antiviral immune receptors in focus. Ann. Bot. 2017;119:711–723. doi: 10.1093/aob/mcw200 27780814
55. Matzke MA, Mosher RA. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat. Rev. Genet. 2014;15:394–408. doi: 10.1038/nrg3683 24805120
56. Wang MB, Masuta C, Smith NA, Shimura H. RNA silencing and plant viral diseases. Mol. Plant Microbe Interact. 2012;25:1275–85. doi: 10.1094/MPMI-04-12-0093-CR 22670757
57. Wang Y, Wu Y, Gong Q, Ismayil A, Yuan Y, Lian B, et al. Geminiviral V2 Protein Suppresses Transcriptional Gene Silencing through Interaction with AGO4. J. Virol. 2019;93:e01675–18. doi: 10.1128/JVI.01675-18 30626668
58. Dowen RH, Pelizzola M, Schmitz RJ, Lister R, Dowen JM, Nery JR, et al. Widespread dynamic DNA methylation in response to biotic stress. Proc. Natl. Acad. Sci. U.S.A. 2012;109:E2183–91. doi: 10.1073/pnas.1209329109 22733782
59. López A, Ramírez V, García-Andrade J, Flors V, Vera P. The RNA silencing enzyme RNA polymerase v is required for plant immunity. PLoS Genet. 2011;7:e1002434. doi: 10.1371/journal.pgen.1002434 22242006
60. Rasmann S, De Vos M, Casteel CL, Tian D, Halitschke R, Sun JY, et al. Herbivory in the previous generation primes plants for enhanced insect resistance. Plant Physiol. 2012;158:854–63. doi: 10.1104/pp.111.187831 22209873
61. Gohlke J, Scholz CJ, Kneitz S, Weber D, Fuchs J, Hedrich R, et al. DNA methylation mediated control of gene expression is critical for development of crown gall tumors. PLoS Genet. 2013;9:e1003267. doi: 10.1371/journal.pgen.1003267 23408907
62. Espinas NA, Saze H, Saijo Y. Epigenetic Control of Defense Signaling and Priming in Plants. Front Plant Sci. 2016;7:1201. doi: 10.3389/fpls.2016.01201 27563304
63. Aufsatz W, Mette MF, van der Winden J, Matzke AJ, Matzke M. RNA-directed DNA methylation in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 2002;99 Suppl 4:16499–506. doi: 10.1073/pnas.162371499 12169664
64. Matzke MA, Primig M, Trnovsky J, Matzke AJ. Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants. EMBO J. 1989;8:643–9. doi: 10.1002/j.1460-2075.1989.tb03421.x 16453872
65. Gutzat R, Mittelsten Scheid O. Epigenetic responses to stress: triple defense? Curr. Opin. Plant Biol. 2012;15:568–73. doi: 10.1016/j.pbi.2012.08.007 22960026
66. Boyko A, Blevins T, Yao Y, Golubov A, Bilichak A, Ilnytskyy Y, et al. Transgenerational adaptation of Arabidopsis to stress requires DNA methylation and the function of Dicer-like proteins. PLoS ONE. 2010;5:e9514. doi: 10.1371/journal.pone.0009514 20209086
67. Mermigka G, Verret F, Kalantidis K. RNA silencing movement in plants. J Integr Plant Biol. 2016;58:328–42. doi: 10.1111/jipb.12423 26297506
68. Lewsey MG, Hardcastle TJ, Melnyk CW, Molnar A, Valli A, Urich MA, et al. Mobile small RNAs regulate genome-wide DNA methylation. Proc. Natl. Acad. Sci. U.S.A. 2016;113:E801–10. doi: 10.1073/pnas.1515072113 26787884
69. Tamiru M, Hardcastle TJ, Lewsey MG. Regulation of genome-wide DNA methylation by mobile small RNAs. New Phytol. 2018;217:540–546. doi: 10.1111/nph.14874 29105762
70. Molnar A, Melnyk CW, Bassett A, Hardcastle TJ, Dunn R, Baulcombe DC. Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells. Science. 2010;328:872–5. doi: 10.1126/science.1187959 20413459
71. Bai S, Kasai A, Yamada K, Li T, Harada T. A mobile signal transported over a long distance induces systemic transcriptional gene silencing in a grafted partner. J. Exp. Bot. 2011;62:4561–70. doi: 10.1093/jxb/err163 21652532
72. Zhang W, Kollwig G, Stecyk E, Apelt F, Dirks R, Kragler F. Graft-transmissible movement of inverted-repeat-induced siRNA signals into flowers. Plant J. 2014;80:106–21. doi: 10.1111/tpj.12622 25039964
73. Parent JS, Martínez de Alba AE, Vaucheret H. The origin and effect of small RNA signaling in plants. Front Plant Sci. 2012;3:179. doi: 10.3389/fpls.2012.00179 22908024
74. Stroud H, Do T, Du J, Zhong X, Feng S, Johnson L, et al. Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nat. Struct. Mol. Biol. 2014;21:64–72. doi: 10.1038/nsmb.2735 24336224
75. Bewick AJ, Niederhuth CE, Ji L, Rohr NA, Griffin PT, Leebens-Mack J, et al. The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants. Genome Biol. 2017;18:65. doi: 10.1186/s13059-017-1195-1 28457232
76. Bartels A, Han Q, Nair P, Stacey L, Gaynier H, Mosley M, et al. Dynamic DNA Methylation in Plant Growth and Development. Int J Mol Sci. 2018;19:2144. doi: 10.3390/ijms19072144 30041459
77. Wendte JM, Schmitz RJ. Specifications of Targeting Heterochromatin Modifications in Plants. Mol Plant. 2018;11:381–387. doi: 10.1016/j.molp.2017.10.002 29032247
78. Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat. Rev. Genet. 2010;11:204–20. doi: 10.1038/nrg2719 20142834
79. Cuerda-Gil D, Slotkin RK. Non-canonical RNA-directed DNA methylation. Nat Plants. 2016;2:16163. doi: 10.1038/nplants.2016.163 27808230
80. Matzke MA, Kanno T, Matzke AJ. RNA-Directed DNA Methylation: The Evolution of a Complex Epigenetic Pathway in Flowering Plants. Annu Rev Plant Biol. 2015;66:243–67. doi: 10.1146/annurev-arplant-043014-114633 25494460
81. Wendte JM, Pikaard CS. The RNAs of RNA-directed DNA methylation. Biochim Biophys Acta Gene Regul Mech. 2017;1860:140–148. doi: 10.1016/j.bbagrm.2016.08.004 27521981
82. Zhai J, Bischof S, Wang H, Feng S, Lee TF, Teng C, et al. A One Precursor One siRNA Model for Pol IV-Dependent siRNA Biogenesis. Cell. 2015;163:445–55. doi: 10.1016/j.cell.2015.09.032 26451488
83. Blevins T, Podicheti R, Mishra V, Marasco M, Wang J, Rusch D, et al. Identification of Pol IV and RDR2-dependent precursors of 24 nt siRNAs guiding de novo DNA methylation in Arabidopsis. Elife. 2015;4:e09591. doi: 10.7554/eLife.09591 26430765
84. Singh J, Mishra V, Wang F, Huang HY, Pikaard CS. Reaction Mechanisms of Pol IV, RDR2, and DCL3 Drive RNA Channeling in the siRNA-Directed DNA Methylation Pathway. Mol. Cell. 2019;75:576–589.e5. doi: 10.1016/j.molcel.2019.07.008 31398324
85. Panda K, Ji L, Neumann DA, Daron J, Schmitz RJ, Slotkin RK. Full-length autonomous transposable elements are preferentially targeted by expression-dependent forms of RNA-directed DNA methylation. Genome Biol. 2016;17:170. doi: 10.1186/s13059-016-1032-y 27506905
86. Zhang Z, Liu X, Guo X, Wang XJ, Zhang X. Arabidopsis AGO3 predominantly recruits 24-nt small RNAs to regulate epigenetic silencing. Nat Plants. 2016;2:16049. doi: 10.1038/nplants.2016.49 27243648
87. Meister G. Argonaute proteins: functional insights and emerging roles. Nat. Rev. Genet. 2013;14:447–59. doi: 10.1038/nrg3462 23732335
88. Wierzbicki AT, Haag JR, Pikaard CS. Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes. Cell. 2008;135:635–48. doi: 10.1016/j.cell.2008.09.035 19013275
89. Cao X, Jacobsen SE. Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr. Biol. 2002;12:1138–44. doi: 10.1016/s0960-9822(02)00925-9 12121623
90. Gallego-Bartolomé J, Liu W, Kuo PH, Feng S, Ghoshal B, Gardiner J, et al. Co-targeting RNA Polymerases IV and V Promotes Efficient De Novo DNA Methylation in Arabidopsis. Cell. 2019;176:1068–1082.e19. doi: 10.1016/j.cell.2019.01.029 30739798
91. Voinnet O. Use, tolerance and avoidance of amplified RNA silencing by plants. Trends Plant Sci. 2008;13:317–28. doi: 10.1016/j.tplants.2008.05.004 18565786
92. Pontier D, Picart C, Roudier F, Garcia D, Lahmy S, Azevedo J, et al. NERD, a plant-specific GW protein, defines an additional RNAi-dependent chromatin-based pathway in Arabidopsis. Mol. Cell. 2012;48:121–32. doi: 10.1016/j.molcel.2012.07.027 22940247
93. Haag JR, Pikaard CS. Multisubunit RNA polymerases IV and V: purveyors of non-coding RNA for plant gene silencing. Nat. Rev. Mol. Cell Biol. 2011;12:483–92. doi: 10.1038/nrm3152 21779025
94. Zhou M, Law JA. RNA Pol IV and V in gene silencing: Rebel polymerases evolving away from Pol II's rules. Curr. Opin. Plant Biol. 2015;27:154–64. doi: 10.1016/j.pbi.2015.07.005 26344361
95. Lahmy S, Pontier D, Bies-Etheve N, Laudié M, Feng S, Jobet E, et al. Evidence for ARGONAUTE4-DNA interactions in RNA-directed DNA methylation in plants. Genes Dev. 2016;30:2565–2570. doi: 10.1101/gad.289553.116 27986858
96. Henderson IR, Zhang X, Lu C, Johnson L, Meyers BC, Green PJ, et al. Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning. Nat. Genet. 2006;38:721–5. doi: 10.1038/ng1804 16699516
97. Bologna NG, Voinnet O. The diversity, biogenesis, and activities of endogenous silencing small RNAs in Arabidopsis. Annu Rev Plant Biol. 2014;65:473–503. doi: 10.1146/annurev-arplant-050213-035728 24579988
98. Wang J, Mei J, Ren G. Plant microRNAs: Biogenesis, Homeostasis, and Degradation. Front Plant Sci. 2019;10:360. doi: 10.3389/fpls.2019.00360 30972093
99. Stroud H, Greenberg MV, Feng S, Bernatavichute YV, Jacobsen SE. Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell. 2013;152:352–64. doi: 10.1016/j.cell.2012.10.054 23313553
100. Fang X, Qi Y. RNAi in Plants: An Argonaute-Centered View. Plant Cell. 2016;28:272–85. doi: 10.1105/tpc.15.00920 26869699
101. Eun C, Lorkovic ZJ, Naumann U, Long Q, Havecker ER, Simon SA, et al. AGO6 functions in RNA-mediated transcriptional gene silencing in shoot and root meristems in Arabidopsis thaliana. PLoS ONE. 2011;6:e25730. doi: 10.1371/journal.pone.0025730 21998686
102. Durán-Figueroa N, Vielle-Calzada JP. ARGONAUTE9-dependent silencing of transposable elements in pericentromeric regions of Arabidopsis. Plant Signal Behav. 2010;5:1476–9. doi: 10.4161/psb.5.11.13548 21057207
103. Cao X, Aufsatz W, Zilberman D, Mette MF, Huang MS, Matzke M, et al. Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation. Curr. Biol. 2003;13:2212–7. doi: 10.1016/j.cub.2003.11.052 14680640
104. Law JA, Vashisht AA, Wohlschlegel JA, Jacobsen SE. SHH1, a homeodomain protein required for DNA methylation, as well as RDR2, RDM4, and chromatin remodeling factors, associate with RNA polymerase IV. PLoS Genet. 2011;7:e1002195. doi: 10.1371/journal.pgen.1002195 21811420
105. Zhang H, Ma ZY, Zeng L, Tanaka K, Zhang CJ, Ma J, et al. DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV. Proc. Natl. Acad. Sci. U.S.A. 2013;110:8290–5. doi: 10.1073/pnas.1300585110 23637343
106. Law JA, Du J, Hale CJ, Feng S, Krajewski K, Palanca AM, et al. Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1. Nature. 2013;498:385–9. doi: 10.1038/nature12178 23636332
107. Zhou M, Palanca AMS, Law JA. Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family. Nat. Genet. 2018;50:865–873. doi: 10.1038/s41588-018-0115-y 29736015
108. Yang DL, Zhang G, Wang L, Li J, Xu D, Di C, et al. Four putative SWI2/SNF2 chromatin remodelers have dual roles in regulating DNA methylation in Arabidopsis. Cell Discov. 2018;4:55. doi: 10.1038/s41421-018-0056-8 30345072
109. Ji L, Chen X. Regulation of small RNA stability: methylation and beyond. Cell Res. 2012;22:624–36. doi: 10.1038/cr.2012.36 22410795
110. Liu ZW, Shao CR, Zhang CJ, Zhou JX, Zhang SW, Li L, et al. The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci. PLoS Genet. 2014;10:e1003948. doi: 10.1371/journal.pgen.1003948 24465213
111. Wierzbicki AT, Ream TS, Haag JR, Pikaard CS. RNA polymerase V transcription guides ARGONAUTE4 to chromatin. Nat. Genet. 2009;41:630–4. doi: 10.1038/ng.365 19377477
112. Zhong X, Hale CJ, Law JA, Johnson LM, Feng S, Tu A, et al. DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons. Nat. Struct. Mol. Biol. 2012;19:870–5. doi: 10.1038/nsmb.2354 22864289
113. Pikaard CS, Haag JR, Pontes OM, Blevins T, Cocklin R. A transcription fork model for Pol IV and Pol V-dependent RNA-directed DNA methylation. Cold Spring Harb. Symp. Quant. Biol. 2012;77:205–12. doi: 10.1101/sqb.2013.77.014803 23567894
114. He XJ, Hsu YF, Zhu S, Wierzbicki AT, Pontes O, Pikaard CS, et al. An effector of RNA-directed DNA methylation in arabidopsis is an ARGONAUTE 4- and RNA-binding protein. Cell. 2009;137:498–508. doi: 10.1016/j.cell.2009.04.028 19410546
115. Liu W, Duttke SH, Hetzel J, Groth M, Feng S, Gallego-Bartolome J, et al. RNA-directed DNA methylation involves co-transcriptional small-RNA-guided slicing of polymerase V transcripts in Arabidopsis. Nat Plants. 2018;4:181–188. doi: 10.1038/s41477-017-0100-y 29379150
116. Zhu Y, Rowley MJ, Böhmdorfer G, Wierzbicki AT. A SWI/SNF chromatin-remodeling complex acts in noncoding RNA-mediated transcriptional silencing. Mol. Cell. 2013;49:298–309. doi: 10.1016/j.molcel.2012.11.011 23246435
117. Ausin I, Mockler TC, Chory J, Jacobsen SE. IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana. Nat. Struct. Mol. Biol. 2009;16:1325–7. doi: 10.1038/nsmb.1690 19915591
118. Xie M, Ren G, Zhang C, Yu B. The DNA- and RNA-binding protein FACTOR of DNA METHYLATION 1 requires XH domain-mediated complex formation for its function in RNA-directed DNA methylation. Plant J. 2012;72:491–500. doi: 10.1111/j.1365-313X.2012.05092.x 22757778
119. Jullien PE, Susaki D, Yelagandula R, Higashiyama T, Berger F. DNA methylation dynamics during sexual reproduction in Arabidopsis thaliana. Curr. Biol. 2012;22:1825–30. doi: 10.1016/j.cub.2012.07.061 22940470
120. Blevins T, Pontvianne F, Cocklin R, Podicheti R, Chandrasekhara C, Yerneni S, et al. A two-step process for epigenetic inheritance in Arabidopsis. Mol. Cell. 2014;54:30–42. doi: 10.1016/j.molcel.2014.02.019 24657166
121. Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell. 2003;12:1577–89. doi: 10.1016/s1097-2765(03)00477-5 14690609
122. Jackson JP, Johnson L, Jasencakova Z, Zhang X, PerezBurgos L, Singh PB, et al. Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma. 2004;112:308–15. doi: 10.1007/s00412-004-0275-7 15014946
123. Du J, Johnson LM, Jacobsen SE, Patel DJ. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 2015;16:519–32. doi: 10.1038/nrm4043 26296162
124. Li X, Harris CJ, Zhong Z, Chen W, Liu R, Jia B, et al. Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation. Proc. Natl. Acad. Sci. U.S.A. 2018;115:E8793–E8802. doi: 10.1073/pnas.1809841115 30150382
125. Du J, Zhong X, Bernatavichute YV, Stroud H, Feng S, Caro E, et al. Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell. 2012;151:167–80. doi: 10.1016/j.cell.2012.07.034 23021223
126. Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. 2001;410:116–20. doi: 10.1038/35065132 11242053
127. Mylne JS, Barrett L, Tessadori F, Mesnage S, Johnson L, Bernatavichute YV, et al. LHP1, the Arabidopsis homologue of HETEROCHROMATIN PROTEIN1, is required for epigenetic silencing of FLC. Proc. Natl. Acad. Sci. U.S.A. 2006;103:5012–7. doi: 10.1073/pnas.0507427103 16549797
128. Zhao S, Cheng L, Gao Y, Zhang B, Zheng X, Wang L, et al. Plant HP1 protein ADCP1 links multivalent H3K9 methylation readout to heterochromatin formation. Cell Res. 2019;29:54–66. doi: 10.1038/s41422-018-0104-9 30425322
129. Klemm SL, Shipony Z, Greenleaf WJ. Chromatin accessibility and the regulatory epigenome. Nat. Rev. Genet. 2019;20:207–220. doi: 10.1038/s41576-018-0089-8 30675018
130. Vongs A, Kakutani T, Martienssen RA, Richards EJ. Arabidopsis thaliana DNA methylation mutants. Science. 1993;260:1926–8. doi: 10.1126/science.8316832 8316832
131. Jeddeloh JA, Stokes TL, Richards EJ. Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nat. Genet. 1999;22:94–7. doi: 10.1038/8803 10319870
132. Kankel MW, Ramsey DE, Stokes TL, Flowers SK, Haag JR, Jeddeloh JA, et al. Arabidopsis MET1 cytosine methyltransferase mutants. Genetics. 2003;163:1109–22. 12663548
133. Jones L, Ratcliff F, Baulcombe DC. RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance. Curr. Biol. 2001;11:747–57. doi: 10.1016/s0960-9822(01)00226-3 11378384
134. Chan SW, Henderson IR, Jacobsen SE. Gardening the genome: DNA methylation in Arabidopsis thaliana. Nat. Rev. Genet. 2005;6:351–60. doi: 10.1038/nrg1601 15861207
135. Li Y, Kumar S, Qian W. Active DNA demethylation: mechanism and role in plant development. Plant Cell Rep. 2018;37:77–85. doi: 10.1007/s00299-017-2215-z 29026973
136. Choi Y, Gehring M, Johnson L, Hannon M, Harada JJ, Goldberg RB, et al. DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis. Cell. 2002;110:33–42. doi: 10.1016/s0092-8674(02)00807-3 12150995
137. Zhu J, Kapoor A, Sridhar VV, Agius F, Zhu JK. The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis. Curr. Biol. 2007;17:54–9. doi: 10.1016/j.cub.2006.10.059 17208187
138. Williams BP, Gehring M. Stable transgenerational epigenetic inheritance requires a DNA methylation-sensing circuit. Nat Commun. 2017;8:2124. doi: 10.1038/s41467-017-02219-3 29242626
139. Wang J, Blevins T, Podicheti R, Haag JR, Tan EH, Wang F, et al. Mutation of Arabidopsis SMC4 identifies condensin as a corepressor of pericentromeric transposons and conditionally expressed genes. Genes Dev. 2017;31:1601–1614. doi: 10.1101/gad.301499.117 28882854
140. Córdoba-Cañero D, Cognat V, Ariza RR, Roldán Arjona T, Molinier J. Dual control of ROS1-mediated active DNA demethylation by DNA damage-binding protein 2 (DDB2). Plant J. 2017;92:1170–1181. doi: 10.1111/tpj.13753 29078035
141. Ream TS, Haag JR, Wierzbicki AT, Nicora CD, Norbeck AD, Zhu JK, et al. Subunit compositions of the RNA-silencing enzymes Pol IV and Pol V reveal their origins as specialized forms of RNA polymerase II. Mol. Cell. 2009;33:192–203. doi: 10.1016/j.molcel.2008.12.015 19110459
142. Huang Y, Kendall T, Forsythe ES, Dorantes-Acosta A, Li S, Caballero-Pérez J, et al. Ancient Origin and Recent Innovations of RNA Polymerase IV and V. Mol. Biol. Evol. 2015;32:1788–99. doi: 10.1093/molbev/msv060 25767205
143. Tucker SL, Reece J, Ream TS, Pikaard CS. Evolutionary history of plant multisubunit RNA polymerases IV and V: subunit origins via genome-wide and segmental gene duplications, retrotransposition, and lineage-specific subfunctionalization. Cold Spring Harb. Symp. Quant. Biol. 2010;75:285–97. doi: 10.1101/sqb.2010.75.037 21447813
144. Luo J, Hall BD. A multistep process gave rise to RNA polymerase IV of land plants. J. Mol. Evol. 2007;64:101–12. doi: 10.1007/s00239-006-0093-z 17160640
145. Haag JR, Brower-Toland B, Krieger EK, Sidorenko L, Nicora CD, Norbeck AD, et al. Functional diversification of maize RNA polymerase IV and V subtypes via alternative catalytic subunits. Cell Rep. 2014;9:378–390. doi: 10.1016/j.celrep.2014.08.067 25284785
146. Ma L, Hatlen A, Kelly LJ, Becher H, Wang W, Kovarik A, et al. Angiosperms Are Unique among Land Plant Lineages in the Occurrence of Key Genes in the RNA-Directed DNA Methylation (RdDM) Pathway. Genome Biol Evol. 2015;7:2648–62. doi: 10.1093/gbe/evv171 26338185
147. Yaari R, Katz A, Domb K, Harris KD, Zemach A, Ohad N. RdDM-independent de novo and heterochromatin DNA methylation by plant CMT and DNMT3 orthologs. Nat Commun. 2019;10:1613. doi: 10.1038/s41467-019-09496-0 30962443
148. Moran Y, Agron M, Praher D, Technau U. The evolutionary origin of plant and animal microRNAs. Nat Ecol Evol. 2017;1:27. doi: 10.1038/s41559-016-0027 28529980
149. Castel SE, Martienssen RA. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat. Rev. Genet. 2013;14:100–12. doi: 10.1038/nrg3355 23329111
150. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science. 2002;297:1833–7. doi: 10.1126/science.1074973 12193640
151. Bühler M, Verdel A, Moazed D. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell. 2006;125:873–86. doi: 10.1016/j.cell.2006.04.025 16751098
152. Zaratiegui M, Castel SE, Irvine DV, Kloc A, Ren J, Li F, et al. RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II. Nature. 2011;479:135–8. doi: 10.1038/nature10501 22002604
153. Fagard M, Vaucheret H. (TRANS)GENE SILENCING IN PLANTS: How Many Mechanisms? Annu. Rev. Plant Physiol. Plant Mol. Biol. 2000;51:167–194. doi: 10.1146/annurev.arplant.51.1.167 15012190
154. Napoli C, Lemieux C, Jorgensen R. Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. Plant Cell. 1990;2:279–289. doi: 10.1105/tpc.2.4.279 12354959
155. van der Krol AR, Mur LA, Beld M, Mol JN, Stuitje AR. Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell. 1990;2:291–9. doi: 10.1105/tpc.2.4.291 2152117
156. Depicker A, Montagu MV. Post-transcriptional gene silencing in plants. Curr. Opin. Cell Biol. 1997;9:373–82. doi: 10.1016/s0955-0674(97)80010-5 9159078
157. Assaad FF, Tucker KL, Signer ER. Epigenetic repeat-induced gene silencing (RIGS) in Arabidopsis. Plant Mol. Biol. 1993;22:1067–85. doi: 10.1007/BF00028978 8400126
158. Ingelbrecht I, Van Houdt H, Van Montagu M, Depicker A. Posttranscriptional silencing of reporter transgenes in tobacco correlates with DNA methylation. Proc. Natl. Acad. Sci. U.S.A. 1994;91:10502–6. doi: 10.1073/pnas.91.22.10502 7937983
159. Meyer P, Heidmann I. Epigenetic variants of a transgenic petunia line show hypermethylation in transgene DNA: an indication for specific recognition of foreign DNA in transgenic plants. Mol. Gen. Genet. 1994;243:390–9. doi: 10.1007/BF00280469 8202084
160. Greenberg MV, Ausin I, Chan SW, Cokus SJ, Cuperus JT, Feng S, et al. Identification of genes required for de novo DNA methylation in Arabidopsis. Epigenetics. 2011;6:344–54. doi: 10.4161/epi.6.3.14242 21150311
161. Meyer P. Transgenes and their contributions to epigenetic research. Int. J. Dev. Biol. 2013;57:509–15. doi: 10.1387/ijdb.120254pm 24166433
162. Hamilton AJ, Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science. 1999;286:950–2. doi: 10.1126/science.286.5441.950 10542148
163. Mette MF, Aufsatz W, van der Winden J, Matzke MA, Matzke AJ. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J. 2000;19:5194–201. doi: 10.1093/emboj/19.19.5194 11013221
164. Hamilton A, Voinnet O, Chappell L, Baulcombe D. Two classes of short interfering RNA in RNA silencing. EMBO J. 2002;21:4671–9. doi: 10.1093/emboj/cdf464 12198169
165. Xie Z, Johansen LK, Gustafson AM, Kasschau KD, Lellis AD, Zilberman D, et al. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol. 2004;2:E104. doi: 10.1371/journal.pbio.0020104 15024409
166. Zilberman D, Cao X, Jacobsen SE. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science. 2003;299:716–9. doi: 10.1126/science.1079695 12522258
167. Dalmay T, Hamilton A, Rudd S, Angell S, Baulcombe DC. An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell. 2000;101:543–53. doi: 10.1016/s0092-8674(00)80864-8 10850496
168. Herr AJ, Jensen MB, Dalmay T, Baulcombe DC. RNA polymerase IV directs silencing of endogenous DNA. Science. 2005;308:118–20. doi: 10.1126/science.1106910 15692015
169. Onodera Y, Haag JR, Ream T, Costa Nunes P, Pontes O, Pikaard CS. Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell. 2005;120:613–22. doi: 10.1016/j.cell.2005.02.007 15766525
170. Kanno T, Huettel B, Mette MF, Aufsatz W, Jaligot E, Daxinger L, et al. Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nat. Genet. 2005;37:761–5. doi: 10.1038/ng1580 15924141
171. Pontier D, Yahubyan G, Vega D, Bulski A, Saez-Vasquez J, Hakimi MA, et al. Reinforcement of silencing at transposons and highly repeated sequences requires the concerted action of two distinct RNA polymerases IV in Arabidopsis. Genes Dev. 2005;19:2030–40. doi: 10.1101/gad.348405 16140984
172. Bond DM, Baulcombe DC. Epigenetic transitions leading to heritable, RNA-mediated de novo silencing in Arabidopsis thaliana. Proc. Natl. Acad. Sci. U.S.A. 2015;112:917–22. doi: 10.1073/pnas.1413053112 25561534
173. Kanazawa A, Inaba JI, Shimura H, Otagaki S, Tsukahara S, Matsuzawa A, et al. Virus-mediated efficient induction of epigenetic modifications of endogenous genes with phenotypic changes in plants. Plant J. 2011;65:156–168. doi: 10.1111/j.1365-313X.2010.04401.x 21175898
174. Dalakouras A, Moser M, Zwiebel M, Krczal G, Hell R, Wassenegger M. A hairpin RNA construct residing in an intron efficiently triggered RNA-directed DNA methylation in tobacco. Plant J. 2009;60:840–51. doi: 10.1111/j.1365-313X.2009.04003.x 19702668
175. Pignatta D, Novitzky K, Satyaki PRV, Gehring M. A variably imprinted epiallele impacts seed development. PLoS Genet. 2018;14:e1007469. doi: 10.1371/journal.pgen.1007469 30395602
176. Papikian A, Liu W, Gallego-Bartolomé J, Jacobsen SE. Site-specific manipulation of Arabidopsis loci using CRISPR-Cas9 SunTag systems. Nat Commun. 2019;10:729. doi: 10.1038/s41467-019-08736-7 30760722
177. Dalakouras A, Wassenegger M, Dadami E, Ganopoulos I, Pappas M, Papadopoulou KK. GMO-free RNAi: exogenous application of RNA molecules in plants. Plant Physiol. 2019;182:38–50. doi: 10.1104/pp.19.00570 31285292
178. Regalado A. The Next Great GMO Debate. MIT Technology Review. 2015. Available from https://www.technologyreview.com/s/540136/the-next-great-gmo-debate/.
179. Gohlke J, Mosher RA. Exploiting mobile RNA silencing for crop improvement. Am. J. Bot. 2015;102:1399–400. doi: 10.3732/ajb.1500173 26391704
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