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RNA Interference in Fungi: Retention and Loss

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  • Authors: Francisco E. Nicolás1, Victoriano Garre2
  • Editor: Joseph Heitman3
    Affiliations: 1: Department of Genetics and Microbiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain; 2: Department of Genetics and Microbiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain; 3: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
  • Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0008-2016
  • Received 20 April 2016 Accepted 07 August 2016 Published 18 November 2016
  • Victoriano Garre, vgarre@um.es
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  • Abstract:

    RNA interference (RNAi) is a mechanism conserved in eukaryotes, including fungi, that represses gene expression by means of small noncoding RNAs (sRNAs) of about 20 to 30 nucleotides. Its discovery is one of the most important scientific breakthroughs of the past 20 years, and it has revolutionized our perception of the functioning of the cell. Initially described and characterized in , the RNAi is widespread in fungi, suggesting that it plays important functions in the fungal kingdom. Several RNAi-related mechanisms for maintenance of genome integrity, particularly protection against exogenous nucleic acids such as mobile elements, have been described in several fungi, suggesting that this is the main function of RNAi in the fungal kingdom. However, an increasing number of fungal sRNAs with regulatory functions generated by specific RNAi pathways have been identified. Several mechanistic aspects of the biogenesis of these sRNAs are known, but their function in fungal development and physiology is scarce, except for remarkable examples such as , in which specific sRNAs clearly regulate responses to environmental and endogenous signals. Despite the retention of RNAi in most species, some fungal groups and species lack an active RNAi mechanism, suggesting that its loss may provide some selective advantage. This article summarizes the current understanding of RNAi functions in the fungal kingdom.

  • Citation: Nicolás F, Garre V. 2016. RNA Interference in Fungi: Retention and Loss. Microbiol Spectrum 4(6):FUNK-0008-2016. doi:10.1128/microbiolspec.FUNK-0008-2016.

Key Concept Ranking

Mobile Genetic Elements
Infection and Immunity
RNA Polymerase II
Fungal Proteins


1. Angenent GC, Franken J, Busscher M, Weiss D, van Tunen AJ. 1994. Co-suppression of the petunia homeotic gene fbp2 affects the identity of the generative meristem. Plant J 5:33–44 http://dx.doi.org/10.1046/j.1365-313X.1994.5010033.x.
2. Napoli C, Lemieux C, Jorgensen R. 1990. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2:279–289 http://dx.doi.org/10.1105/tpc.2.4.279.
3. Romano N, Macino G. 1992. Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Mol Microbiol 6:3343–3353 http://dx.doi.org/10.1111/j.1365-2958.1992.tb02202.x.
4. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811 http://dx.doi.org/10.1038/35888.
5. Sen GL, Blau HM. 2006. A brief history of RNAi: the silence of the genes. FASEB J 20:1293–1299 http://dx.doi.org/10.1096/fj.06-6014rev.
6. Nicolás FE, Ruiz-Vázquez RM. 2013. Functional diversity of RNAi-associated sRNAs in fungi. Int J Mol Sci 14:15348–15360 http://dx.doi.org/10.3390/ijms140815348.
7. Nicolas FE, Lopez-Gomollon S, Lopez-Martinez AF, Dalmay T. 2009. RNA silencing: recent developments on miRNAs. Recent Pat DNA Gene Seq 3:77–87 http://dx.doi.org/10.2174/187221509788654197.
8. Alvarez-Fernandez R, Lopez-Gomollon S, Lopez-Martinez AF, Nicolas FE. 2011. Bioengineering RNA silencing across the life kingdoms. Recent Pat Biotechnol 5:118–146 http://dx.doi.org/10.2174/187220811796365680.
9. Cervantes M, Vila A, Nicolás FE, Moxon S, de Haro JP, Dalmay T, Torres-Martínez S, Ruiz-Vázquez RM. 2013. A single argonaute gene participates in exogenous and endogenous RNAi and controls cellular functions in the basal fungus Mucor circinelloides. PLoS One 8:e69283. doi:10.1371/journal.pone.0069283 http://dx.doi.org/10.1371/journal.pone.0069283.
10. Nicolás FE, de Haro JP, Torres-Martínez S, Ruiz-Vázquez RM. 2007. Mutants defective in a Mucor circinelloides dicer-like gene are not compromised in siRNA silencing but display developmental defects. Fungal Genet Biol 44:504–516 http://dx.doi.org/10.1016/j.fgb.2006.09.003.
11. Nicolás FE, Vila A, Moxon S, Cascales MD, Torres-Martínez S, Ruiz-Vázquez RM, Garre V. 2015. The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides. BMC Genomics 16:237. doi:10.1186/s12864-015-1443-2 http://dx.doi.org/10.1186/s12864-015-1443-2.
12. Nicolás FE, Moxon S, de Haro JP, Calo S, Grigoriev IV, Torres-Martínez S, Moulton V, Ruiz-Vázquez RM, Dalmay T. 2010. Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides. Nucleic Acids Res 38:5535–5541 http://dx.doi.org/10.1093/nar/gkq301.
13. Choi J, Kim KT, Jeon J, Wu J, Song H, Asiegbu FO, Lee YH. 2014. funRNA: a fungi-centered genomics platform for genes encoding key components of RNAi. BMC Genomics 15(Suppl 9):S14. doi:10.1186/1471-2164-15-S9-S14 http://dx.doi.org/10.1186/1471-2164-15-S9-S14.
14. Lee HC, Aalto AP, Yang Q, Chang SS, Huang G, Fisher D, Cha J, Poranen MM, Bamford DH, Liu Y. 2010. The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring replication protein A and a DNA helicase. PLoS Biol 8:e1000496. doi:10.1371/journal.pbio.1000496. http://dx.doi.org/10.1371/journal.pbio.1000496.
15. Laurila MR, Salgado PS, Makeyev EV, Nettelship J, Stuart DI, Grimes JM, Bamford DH. 2005. Gene silencing pathway RNA-dependent RNA polymerase of Neurospora crassa: yeast expression and crystallization of selenomethionated QDE-1 protein. J Struct Biol 149:111–115 http://dx.doi.org/10.1016/j.jsb.2004.10.001.
16. Yang Q, Ye QA, Liu Y. 2015. Mechanism of siRNA production from repetitive DNA. Genes Dev 29:526–537 http://dx.doi.org/10.1101/gad.255828.114. [CrossRef]
17. Cogoni C, Macino G. 1999. Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399:166–169 http://dx.doi.org/10.1038/20215.
18. Xie Z, Johansen LK, Gustafson AM, Kasschau KD, Lellis AD, Zilberman D, Jacobsen SE, Carrington JC. 2004. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol 2:e104. doi:10.1371/journal.pbio.0020104 http://dx.doi.org/10.1371/journal.pbio.0020104.
19. Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S, Timmons L, Plasterk RH, Fire A. 2001. On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476 http://dx.doi.org/10.1016/S0092-8674(01)00576-1.
20. Vaistij FE, Jones L, Baulcombe DC. 2002. Spreading of RNA targeting and DNA methylation in RNA silencing requires transcription of the target gene and a putative RNA-dependent RNA polymerase. Plant Cell 14:857–867 http://dx.doi.org/10.1105/tpc.010480.
21. Calo S, Nicolás FE, Vila A, Torres-Martínez S, Ruiz-Vázquez RM. 2012. Two distinct RNA-dependent RNA polymerases are required for initiation and amplification of RNA silencing in the basal fungus Mucor circinelloides. Mol Microbiol 83:379–394 http://dx.doi.org/10.1111/j.1365-2958.2011.07939.x.
22. Goldoni M, Azzalin G, Macino G, Cogoni C. 2004. Efficient gene silencing by expression of double stranded RNA in Neurospora crassa. Fungal Genet Biol 41:1016–1024 http://dx.doi.org/10.1016/j.fgb.2004.08.002.
23. MacRae IJ, Doudna JA. 2007. Ribonuclease revisited: structural insights into ribonuclease III family enzymes. Curr Opin Struct Biol 17:138–145 http://dx.doi.org/10.1016/j.sbi.2006.12.002.
24. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366 http://dx.doi.org/10.1038/35053110.
25. MacRae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA. 2006. Structural basis for double-stranded RNA processing by Dicer. Science 311:195–198 http://dx.doi.org/10.1126/science.1121638.
26. MacRae IJ, Zhou K, Doudna JA. 2007. Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol 14:934–940 http://dx.doi.org/10.1038/nsmb1293.
27. Catalanotto C, Pallotta M, ReFalo P, Sachs MS, Vayssie L, Macino G, Cogoni C. 2004. Redundancy of the two dicer genes in transgene-induced posttranscriptional gene silencing in Neurospora crassa. Mol Cell Biol 24:2536–2545 http://dx.doi.org/10.1128/MCB.24.6.2536-2545.2004.
28. de Haro JP, Calo S, Cervantes M, Nicolás FE, Torres-Martínez S, Ruiz-Vázquez RM. 2009. A single dicer gene is required for efficient gene silencing associated with two classes of small antisense RNAs in Mucor circinelloides. Eukaryot Cell 8:1486–1497 http://dx.doi.org/10.1128/EC.00191-09.
29. Hutvágner G, Zamore PD. 2002. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056–2060 http://dx.doi.org/10.1126/science.1073827.
30. Doench JG, Petersen CP, Sharp PA. 2003. siRNAs can function as miRNAs. Genes Dev 17:438–442 http://dx.doi.org/10.1101/gad.1064703.
31. Jackson RJ, Standart N. 2007. How do microRNAs regulate gene expression? Sci STKE 2007:re1. doi:10.1126/stke.3672007re1 http://dx.doi.org/10.1126/stke.3672007re1.
32. Höck J, Meister G. 2008. The Argonaute protein family. Genome Biol 9:210 http://dx.doi.org/10.1186/gb-2008-9-2-210.
33. Wei KF, Wu LJ, Chen J, Chen YF, Xie DX. 2012. Structural evolution and functional diversification analyses of argonaute protein. J Cell Biochem 113:2576–2585 http://dx.doi.org/10.1002/jcb.24133.
34. Lingel A, Simon B, Izaurralde E, Sattler M. 2003. Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature 426:465–469 http://dx.doi.org/10.1038/nature02123.
35. Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ. 2005. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434:666–670 http://dx.doi.org/10.1038/nature03514.
36. Fagard M, Boutet S, Morel JB, Bellini C, Vaucheret H. 2000. AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. Proc Natl Acad Sci USA 97:11650–11654 http://dx.doi.org/10.1073/pnas.200217597.
37. Lee DW, Pratt RJ, McLaughlin M, Aramayo R. 2003. An argonaute-like protein is required for meiotic silencing. Genetics 164:821–828.
38. Francia S, Michelini F, Saxena A, Tang D, de Hoon M, Anelli V, Mione M, Carninci P, d’Adda di Fagagna F. 2012. Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488:231–235 http://dx.doi.org/10.1038/nature11179.
39. Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD, Carrington JC, Doerge RW, Colot V, Martienssen R. 2004. Role of transposable elements in heterochromatin and epigenetic control. Nature 430:471–476 http://dx.doi.org/10.1038/nature02651.
40. Cogoni C, Macino G. 1997. Isolation of quelling-defective (qde) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa. Proc Natl Acad Sci USA 94:10233–10238 http://dx.doi.org/10.1073/pnas.94.19.10233.
41. Wang X, Wang P, Sun S, Darwiche S, Idnurm A, Heitman J. 2012. Transgene induced co-suppression during vegetative growth in Cryptococcus neoformans. PLoS Genet 8:e1002885. doi:10.1371/journal.pgen.1002885 http://dx.doi.org/10.1371/journal.pgen.1002885.
42. Nicolás FE, Torres-Martínez S, Ruiz-Vázquez RM. 2003. Two classes of small antisense RNAs in fungal RNA silencing triggered by non-integrative transgenes. EMBO J 22:3983–3991 http://dx.doi.org/10.1093/emboj/cdg384.
43. Fulci V, Macino G. 2007. Quelling: post-transcriptional gene silencing guided by small RNAs in Neurospora crassa. Curr Opin Microbiol 10:199–203 http://dx.doi.org/10.1016/j.mib.2007.03.016.
44. Feretzaki M, Billmyre RB, Clancey SA, Wang X, Heitman J. 2016. Gene network polymorphism illuminates loss and retention of novel RNAi silencing components in the Cryptococcus pathogenic species complex. PLoS Genet 12:e1005868. doi:10.1371/journal.pgen.1005868 http://dx.doi.org/10.1371/journal.pgen.1005868.
45. Ruiz-Vázquez RM, Nicolás FE, Torres-Martínez S, Garre V. 2015. Distinct RNAi pathways in the regulation of physiology and development in the fungus Mucor circinelloides. Adv Genet 91:55–102 http://dx.doi.org/10.1016/bs.adgen.2015.07.002.
46. Zhang Z, Chang SS, Zhang Z, Xue Z, Zhang H, Li S, Liu Y. 2013. Homologous recombination as a mechanism to recognize repetitive DNA sequences in an RNAi pathway. Genes Dev 27:145–150 http://dx.doi.org/10.1101/gad.209494.112.
47. Zhang Z, Yang Q, Sun G, Chen S, He Q, Li S, Liu Y. 2014. Histone H3K56 acetylation is required for quelling-induced small RNA production through its role in homologous recombination. J Biol Chem 289:9365–9371 http://dx.doi.org/10.1074/jbc.M113.528521.
48. Cogoni C, Macino G. 1999. Posttranscriptional gene silencing in Neurospora by a RecQ DNA helicase. Science 286:2342–2344 http://dx.doi.org/10.1126/science.286.5448.2342.
49. Cecere G, Cogoni C. 2009. Quelling targets the rDNA locus and functions in rDNA copy number control. BMC Microbiol 9:44. doi:10.1186/1471-2180-9-44 http://dx.doi.org/10.1186/1471-2180-9-44.
50. Lee HC, Chang SS, Choudhary S, Aalto AP, Maiti M, Bamford DH, Liu Y. 2009. qiRNA is a new type of small interfering RNA induced by DNA damage. Nature 459:274–277 http://dx.doi.org/10.1038/nature08041.
51. Bzymek M, Lovett ST. 2001. Instability of repetitive DNA sequences: the role of replication in multiple mechanisms. Proc Natl Acad Sci USA 98:8319–8325 http://dx.doi.org/10.1073/pnas.111008398.
52. Vader G, Blitzblau HG, Tame MA, Falk JE, Curtin L, Hochwagen A. 2011. Protection of repetitive DNA borders from self-induced meiotic instability. Nature 477:115–119 http://dx.doi.org/10.1038/nature10331.
53. Castel SE, Ren J, Bhattacharjee S, Chang AY, Sánchez M, Valbuena A, Antequera F, Martienssen RA. 2014. Dicer promotes transcription termination at sites of replication stress to maintain genome stability. Cell 159:572–583 http://dx.doi.org/10.1016/j.cell.2014.09.031.
54. Ghabrial SA, Castón JR, Jiang D, Nibert ML, Suzuki N. 2015. 50-plus years of fungal viruses. Virology 479-480:356–368 http://dx.doi.org/10.1016/j.virol.2015.02.034.
55. Pearson MN, Beever RE, Boine B, Arthur K. 2009. Mycoviruses of filamentous fungi and their relevance to plant pathology. Mol Plant Pathol 10:115–128 http://dx.doi.org/10.1111/j.1364-3703.2008.00503.x.
56. Segers GC, Zhang X, Deng F, Sun Q, Nuss DL. 2007. Evidence that RNA silencing functions as an antiviral defense mechanism in fungi. Proc Natl Acad Sci USA 104:12902–12906 http://dx.doi.org/10.1073/pnas.0702500104.
57. Sun Q, Choi GH, Nuss DL. 2009. A single Argonaute gene is required for induction of RNA silencing antiviral defense and promotes viral RNA recombination. Proc Natl Acad Sci USA 106:17927–17932 http://dx.doi.org/10.1073/pnas.0907552106.
58. Zhang DX, Spiering MJ, Nuss DL. 2014. Characterizing the roles of Cryphonectria parasitica RNA-dependent RNA polymerase-like genes in antiviral defense, viral recombination and transposon transcript accumulation. PLoS One 9:e108653. doi:10.1371/journal.pone.0108653 http://dx.doi.org/10.1371/journal.pone.0108653.
59. Eusebio-Cope A, Sun L, Tanaka T, Chiba S, Kasahara S, Suzuki N. 2015. The chestnut blight fungus for studies on virus/host and virus/virus interactions: from a natural to a model host. Virology 477:164–175 http://dx.doi.org/10.1016/j.virol.2014.09.024.
60. Wang X, Hsueh YP, Li W, Floyd A, Skalsky R, Heitman J. 2010. Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Genes Dev 24:2566–2582 http://dx.doi.org/10.1101/gad.1970910. [CrossRef]
61. Wang X, Darwiche S, Heitman J. 2013. Sex-induced silencing operates during opposite-sex and unisexual reproduction in Cryptococcus neoformans. Genetics 193:1163–1174 http://dx.doi.org/10.1534/genetics.113.149443.
62. Shiu PK, Metzenberg RL. 2002. Meiotic silencing by unpaired DNA: properties, regulation and suppression. Genetics 161:1483–1495.
63. Jacobson DJ, Raju NB, Freitag M. 2008. Evidence for the absence of meiotic silencing by unpaired DNA in Neurospora tetrasperma. Fungal Genet Biol 45:351–362 http://dx.doi.org/10.1016/j.fgb.2007.09.014.
64. Hammond TM, Xiao H, Boone EC, Decker LM, Lee SA, Perdue TD, Pukkila PJ, Shiu PK. 2013. Novel proteins required for meiotic silencing by unpaired DNA and siRNA generation in Neurospora crassa. Genetics 194:91–100 http://dx.doi.org/10.1534/genetics.112.148999.
65. Samarajeewa DA, Sauls PA, Sharp KJ, Smith ZJ, Xiao H, Groskreutz KM, Malone TL, Boone EC, Edwards KA, Shiu PK, Larson ED, Hammond TM. 2014. Efficient detection of unpaired DNA requires a member of the rad54-like family of homologous recombination proteins. Genetics 198:895–904 http://dx.doi.org/10.1534/genetics.114.168187.
66. Decker LM, Boone EC, Xiao H, Shanker BS, Boone SF, Kingston SL, Lee SA, Hammond TM, Shiu PK. 2015. Complex formation of RNA silencing proteins in the perinuclear region of Neurospora crassa. Genetics 199:1017–1021 http://dx.doi.org/10.1534/genetics.115.174623.
67. Chang SS, Zhang Z, Liu Y. 2012. RNA interference pathways in fungi: mechanisms and functions. Annu Rev Microbiol 66:305–323 http://dx.doi.org/10.1146/annurev-micro-092611-150138.
68. Hu Y, Stenlid J, Elfstrand M, Olson A. 2013. Evolution of RNA interference proteins dicer and argonaute in Basidiomycota. Mycologia 105:1489–1498 http://dx.doi.org/10.3852/13-171.
69. Garre V, Nicolás FE, Torres-Martínez S, Ruiz-Vázquez RM. 2014. The RNAi machinery in Mucorales: the emerging role of endogenous small RNAs, p 291–313. In Sesma A, von der Haar T (ed), Fungal RNA Biology. Springer International Publishing, Cham, Switzerland. http://dx.doi.org/10.1007/978-3-319-05687-6_12
70. Turner JM, Mahadevaiah SK, Fernandez-Capetillo O, Nussenzweig A, Xu X, Deng CX, Burgoyne PS. 2005. Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 37:41–47.
71. Duan G, Saint RB, Helliwell CA, Behm CA, Wang MB, Waterhouse PM, Gordon KH. 2013. C. elegans RNA-dependent RNA polymerases rrf-1 and ego-1 silence Drosophila transgenes by differing mechanisms. Cell Mol Life Sci 70:1469–1481 http://dx.doi.org/10.1007/s00018-012-1218-8.
72. Girard A, Hannon GJ. 2008. Conserved themes in small-RNA-mediated transposon control. Trends Cell Biol 18:136–148 http://dx.doi.org/10.1016/j.tcb.2008.01.004.
73. Wang Y, Smith KM, Taylor JW, Freitag M, Stajich JE. 2015. Endogenous small RNA mediates meiotic silencing of a novel DNA transposon. G3 (Bethesda) 5:1949–1960 http://dx.doi.org/10.1534/g3.115.017921.
74. Grewal SI, Elgin SC. 2007. Transcription and RNA interference in the formation of heterochromatin. Nature 447:399–406 http://dx.doi.org/10.1038/nature05914.
75. Pidoux AL, Allshire RC. 2004. Kinetochore and heterochromatin domains of the fission yeast centromere. Chromosome Res 12:521–534 http://dx.doi.org/10.1023/B:CHRO.0000036586.81775.8b.
76. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. 2002. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837 http://dx.doi.org/10.1126/science.1074973.
77. Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D. 2004. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802 http://dx.doi.org/10.1016/j.cell.2004.11.034.
78. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D. 2004. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676 http://dx.doi.org/10.1126/science.1093686.
79. Martienssen R, Moazed D. 2015. RNAi and heterochromatin assembly. Cold Spring Harb Perspect Biol 7:a019323. doi:10.1101/cshperspect.a019323 http://dx.doi.org/10.1101/cshperspect.a019323. [CrossRef]
80. Bayne EH, Portoso M, Kagansky A, Kos-Braun IC, Urano T, Ekwall K, Alves F, Rappsilber J, Allshire RC. 2008. Splicing factors facilitate RNAi-directed silencing in fission yeast. Science 322:602–606 http://dx.doi.org/10.1126/science.1164029.
81. Bayne EH, Bijos DA, White SA, de Lima Alves F, Rappsilber J, Allshire RC. 2014. A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast. Genome Biol 15:481 http://dx.doi.org/10.1186/s13059-014-0481-4.
82. Dumesic PA, Madhani HD. 2013. The spliceosome as a transposon sensor. RNA Biol 10:1653–1660 http://dx.doi.org/10.4161/rna.26800.
83. Volanakis EJ, Boothby MR, Sherr CJ. 2013. Epigenetic regulation of the Ink4a-Arf (Cdkn2a) tumor suppressor locus in the initiation and progression of Notch1-driven T cell acute lymphoblastic leukemia. Exp Hematol 41:377–386 http://dx.doi.org/10.1016/j.exphem.2012.11.006.
84. Ausin I, Greenberg MV, Li CF, Jacobsen SE. 2012. The splicing factor SR45 affects the RNA-directed DNA methylation pathway in Arabidopsis. Epigenetics 7:29–33 http://dx.doi.org/10.4161/epi.7.1.18782.
85. Tabach Y, Billi AC, Hayes GD, Newman MA, Zuk O, Gabel H, Kamath R, Yacoby K, Chapman B, Garcia SM, Borowsky M, Kim JK, Ruvkun G. 2013. Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence. Nature 493:694–698 http://dx.doi.org/10.1038/nature11779.
86. Xiong XP, Kurthkoti K, Chang KY, Lichinchi G, De N, Schneemann A, MacRae IJ, Rana TM, Perrimon N, Zhou R. 2013. Core small nuclear ribonucleoprotein particle splicing factor SmD1 modulates RNA interference in Drosophila. Proc Natl Acad Sci USA 110:16520–16525 http://dx.doi.org/10.1073/pnas.1315803110.
87. Bartel DP. 2009. MicroRNAs: target recognition and regulatory functions. Cell 136:215–233 http://dx.doi.org/10.1016/j.cell.2009.01.002.
88. Lee HC, Li L, Gu W, Xue Z, Crosthwaite SK, Pertsemlidis A, Lewis ZA, Freitag M, Selker EU, Mello CC, Liu Y. 2010. Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi. Mol Cell 38:803–814 http://dx.doi.org/10.1016/j.molcel.2010.04.005.
89. Faghihi MA, Wahlestedt C. 2009. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637–643 http://dx.doi.org/10.1038/nrm2738.
90. Donaldson ME, Saville BJ. 2012. Natural antisense transcripts in fungi. Mol Microbiol 85:405–417 http://dx.doi.org/10.1111/j.1365-2958.2012.08125.x.
91. Drinnenberg IA, Weinberg DE, Xie KT, Mower JP, Wolfe KH, Fink GR, Bartel DP. 2009. RNAi in budding yeast. Science 326:544–550 http://dx.doi.org/10.1126/science.1176945.
92. Dang Y, Li L, Guo W, Xue Z, Liu Y. 2013. Convergent transcription induces dynamic DNA methylation at disiRNA loci. PLoS Genet 9:e1003761. doi:10.1371/journal.pgen.1003761 http://dx.doi.org/10.1371/journal.pgen.1003761.
93. Li N, Joska TM, Ruesch CE, Coster SJ, Belden WJ. 2015. The frequency natural antisense transcript first promotes, then represses, frequency gene expression via facultative heterochromatin. Proc Natl Acad Sci USA 112:4357–4362 http://dx.doi.org/10.1073/pnas.1406130112.
94. Torres-Martínez S, Ruiz-Vázquez RM. 2016. RNAi pathways in Mucor: a tale of proteins, small RNAs and functional diversity. Fungal Genet Biol 90:44–52 http://dx.doi.org/10.1016/j.fgb.2015.11.006.
95. Carreras-Villaseñor N, Esquivel-Naranjo EU, Villalobos-Escobedo JM, Abreu-Goodger C, Herrera-Estrella A. 2013. The RNAi machinery regulates growth and development in the filamentous fungus Trichoderma atroviride. Mol Microbiol 89:96–112 http://dx.doi.org/10.1111/mmi.12261.
96. Trieu TA, Calo S, Nicolás FE, Vila A, Moxon S, Dalmay T, Torres-Martínez S, Garre V, Ruiz-Vázquez RM. 2015. A non-canonical RNA silencing pathway promotes mRNA degradation in basal fungi. PLoS Genet 11:e1005168. doi:10.1371/journal.pgen.1005168 http://dx.doi.org/10.1371/journal.pgen.1005168.
97. Villalobos-Escobedo JM, Herrera-Estrella A, Carreras-Villaseñor N. 2016. The interaction of fungi with the environment orchestrated by RNAi. Mycologia 108:556–571 http://dx.doi.org/10.3852/15-246.
98. Weiberg A, Wang M, Lin FM, Zhao H, Zhang Z, Kaloshian I, Huang HD, Jin H. 2013. Fungal small RNAs suppress plant immunity by hijacking host RNA interference pathways. Science 342:118–123 http://dx.doi.org/10.1126/science.1239705.
99. Knip M, Constantin ME, Thordal-Christensen H. 2014. Trans-kingdom cross-talk: small RNAs on the move. PLoS Genet 10:e1004602. doi:10.1371/journal.pgen.1004602 http://dx.doi.org/10.1371/journal.pgen.1004602.
100. Calo S, Shertz-Wall C, Lee SC, Bastidas RJ, Nicolás FE, Granek JA, Mieczkowski P, Torres-Martínez S, Ruiz-Vázquez RM, Cardenas ME, Heitman J. 2014. Antifungal drug resistance evoked via RNAi-dependent epimutations. Nature 513:555–558 http://dx.doi.org/10.1038/nature13575. [CrossRef]
101. Lee SC, Li A, Calo S, Heitman J. 2013. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides. PLoS Pathog 9:e1003625. doi:10.1371/journal.ppat.1003625 http://dx.doi.org/10.1371/journal.ppat.1003625.
102. Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL. 1991. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807–815 http://dx.doi.org/10.1016/0092-8674(91)90124-H.
103. Drinnenberg IA, Fink GR, Bartel DP. 2011. Compatibility with killer explains the rise of RNAi-deficient fungi. Science 333:1592 http://dx.doi.org/10.1126/science.1209575.
104. Lye LF, Owens K, Shi H, Murta SM, Vieira AC, Turco SJ, Tschudi C, Ullu E, Beverley SM. 2010. Retention and loss of RNA interference pathways in trypanosomatid protozoans. PLoS Pathog 6:e1001161. doi:10.1371/journal.ppat.1001161 http://dx.doi.org/10.1371/journal.ppat.1001161.
105. Robinson KA, Beverley SM. 2003. Improvements in transfection efficiency and tests of RNA interference (RNAi) approaches in the protozoan parasite Leishmania. Mol Biochem Parasitol 128:217–228 http://dx.doi.org/10.1016/S0166-6851(03)00079-3.
106. Lange H, Zuber H, Sement FM, Chicher J, Kuhn L, Hammann P, Brunaud V, Bérard C, Bouteiller N, Balzergue S, Aubourg S, Martin-Magniette ML, Vaucheret H, Gagliardi D. 2014. The RNA helicases AtMTR4 and HEN2 target specific subsets of nuclear transcripts for degradation by the nuclear exosome in Arabidopsis thaliana. PLoS Genet 10:e1004564. doi:10.1371/journal.pgen.1004564 http://dx.doi.org/10.1371/journal.pgen.1004564.
107. Thran M, Link K, Sonnewald U. 2012. The Arabidopsis DCP2 gene is required for proper mRNA turnover and prevents transgene silencing in Arabidopsis. Plant J 72:368–377 http://dx.doi.org/10.1111/j.1365-313X.2012.05066.x.
108. Voinnet O. 2008. Use, tolerance and avoidance of amplified RNA silencing by plants. Trends Plant Sci 13:317–328 http://dx.doi.org/10.1016/j.tplants.2008.05.004.
109. Gazzani S, Lawrenson T, Woodward C, Headon D, Sablowski R. 2004. A link between mRNA turnover and RNA interference in Arabidopsis. Science 306:1046–1048 http://dx.doi.org/10.1126/science.1101092.
110. Luo Z, Chen Z. 2007. Improperly terminated, unpolyadenylated mRNA of sense transgenes is targeted by RDR6-mediated RNA silencing in Arabidopsis. Plant Cell 19:943–958 http://dx.doi.org/10.1105/tpc.106.045724. [CrossRef]
111. Nicolás FE, Torres-Martínez S, Ruiz-Vázquez RM. 2009. Transcriptional activation increases RNA silencing efficiency and stability in the fungus Mucor circinelloides. J Biotechnol 142:123–126 http://dx.doi.org/10.1016/j.jbiotec.2009.04.003.

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RNA interference (RNAi) is a mechanism conserved in eukaryotes, including fungi, that represses gene expression by means of small noncoding RNAs (sRNAs) of about 20 to 30 nucleotides. Its discovery is one of the most important scientific breakthroughs of the past 20 years, and it has revolutionized our perception of the functioning of the cell. Initially described and characterized in , the RNAi is widespread in fungi, suggesting that it plays important functions in the fungal kingdom. Several RNAi-related mechanisms for maintenance of genome integrity, particularly protection against exogenous nucleic acids such as mobile elements, have been described in several fungi, suggesting that this is the main function of RNAi in the fungal kingdom. However, an increasing number of fungal sRNAs with regulatory functions generated by specific RNAi pathways have been identified. Several mechanistic aspects of the biogenesis of these sRNAs are known, but their function in fungal development and physiology is scarce, except for remarkable examples such as , in which specific sRNAs clearly regulate responses to environmental and endogenous signals. Despite the retention of RNAi in most species, some fungal groups and species lack an active RNAi mechanism, suggesting that its loss may provide some selective advantage. This article summarizes the current understanding of RNAi functions in the fungal kingdom.

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Image of FIGURE 1

Main RNA interference (RNAi) pathways identified in . Fungal RNAi-mediated defense mechanisms against exogenous nucleic acids in fungi is exemplified by the defense mechanism (left box). This fungus shows an amplification step mediated by RdRP-2, which has not been found in other fungi. In addition to this defense pathway, this fungus shows two distinct RNAi pathways to regulate the expression of endogenous genes (central and right boxes). Question marks indicate that the R3B2 protein participates in these pathways, although its precise function is unknown.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0008-2016
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