RNA Editing pp 35-50 | Cite as

Discovering RNA Editing Events in Fungi

  • Huiquan LiuEmail author
  • Jin-Rong Xu
Part of the Methods in Molecular Biology book series (MIMB, volume 2181)


RNA editing is an important posttranscriptional process that alters the genetic information of RNA encoded by genomic DNA. Adenosine-to-inosine (A-to-I) editing is the most prevalent type of RNA editing in animal kingdom, catalyzed by adenosine deaminases acting on RNA (ADARs). Recently, genome-wide A-to-I RNA editing is discovered in fungi, involving adenosine deamination mechanisms distinct from animals. Aiming to draw more attention to RNA editing in fungi, here we discuss the considerations for deep sequencing data preparation and the available various methods for detecting RNA editing, with a special emphasis on their usability for fungal RNA editing detection. We describe computational protocols for the identification of candidate RNA editing sites in fungi by using two software packages REDItools and RES-Scanner with RNA sequencing (RNA-Seq) and genomic DNA sequencing (DNA-Seq) data.

Key words

RNA editing A-to-I editing RNA-Seq DNA-Seq RNA modifications Inosine 



This work was supported by grants from the National Science Fund for Excellent Young Scholars (Grant 31622045) and the National Youth Talent Support Program (Z111021802).


  1. 1.
    Knoop V (2011) When you can’t trust the DNA: RNA editing changes transcript sequences. Cell Mol Life Sci 68(4):567–586.  
  2. 2.
    Chateigner-Boutin AL, Small I (2011) Organellar RNA editing. Wiley Interdiscip Rev RNA 2(4):493–506.  
  3. 3.
    Knisbacher BA, Gerber D, Levanon EY (2016) DNA editing by APOBECs: a genomic preserver and transformer. Trends Genet 32(1):16–28.  
  4. 4.
    Nishikura K (2010) Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 79:321–349.  
  5. 5.
    Sakurai M, Ueda H, Yano T, Okada S, Terajima H, Mitsuyama T, Toyoda A, Fujiyama A, Kawabata H, Suzuki T (2014) A biochemical landscape of A-to-I RNA editing in the human brain transcriptome. Genome Res 24(3):522–534.  
  6. 6.
    Cattenoz PB, Taft RJ, Westhof E, Mattick JS (2013) Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage. RNA 19(2):257–270.  
  7. 7.
    Okada S, Ueda H, Noda Y, Suzuki T (2019) Transcriptome-wide identification of A-to-I RNA editing sites using ICE-seq. Methods 156:66–78.  
  8. 8.
    Picardi E, D’Erchia AM, Lo Giudice C, Pesole G (2017) REDIportal: a comprehensive database of A-to-I RNA editing events in humans. Nucleic Acids Res 45(D1):D750–D757.  
  9. 9.
    Kiran AM, O’Mahony JJ, Sanjeev K, Baranov PV (2013) Darned in 2013: inclusion of model organisms and linking with Wikipedia. Nucleic Acids Res 41(Database Issue):D258–D261.  
  10. 10.
    Porath HT, Knisbacher BA, Eisenberg E, Levanon EY (2017) Massive A-to-I RNA editing is common across the Metazoa and correlates with dsRNA abundance. Genome Biol 18(1):185.  
  11. 11.
    Ramaswami G, Li JB (2014) RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res 42(Database issue):D109–D113.  
  12. 12.
    Grice LF, Degnan BM (2015) The origin of the ADAR gene family and animal RNA editing. BMC Evol Biol 15:4.  
  13. 13.
    Liu H, Li Y, Chen D, Qi Z, Wang Q, Wang J, Jiang C, Xu JR (2017) A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa. Proc Natl Acad Sci U S A 114(37):E7756–E7765.  
  14. 14.
    Liu H, Wang Q, He Y, Chen L, Hao C, Jiang C, Li Y, Dai Y, Kang Z, Xu JR (2016) Genome-wide A-to-I RNA editing in fungi independent of ADAR enzymes. Genome Res 26(4):499–509.  
  15. 15.
    Teichert I, Dahlmann TA, Kuck U, Nowrousian M (2017) RNA editing during sexual development occurs in distantly related filamentous ascomycetes. Genome Biol Evol 9(4):855–868.  
  16. 16.
    Wang C, Xu JR, Liu H (2016) A-to-I RNA editing independent of ADARs in filamentous fungi. RNA Biol 13(10):940–945.  
  17. 17.
    Bian Z, Ni Y, Xu JR, Liu H (2019) A-to-I mRNA editing in fungi: occurrence, function, and evolution. Cell Mol Life Sci 76(2):329–340.  
  18. 18.
    Wang Q, Jiang C, Liu H, Xu J-R (2016) ADAR-independent A-to-I RNA editing is generally adaptive for sexual reproduction in Fungi. bioRxiv:059725.  
  19. 19.
    Hao C, Yin J, Sun M, Wang Q, Liang J, Bian Z, Liu H, Xu JR (2019) The meiosis-specific APC activator FgAMA1 is dispensable for meiosis but important for ascosporogenesis in Fusarium graminearum. Mol Microbiol 111(5):1245–1262.  
  20. 20.
    Narasimhan V, Danecek P, Scally A, Xue Y, Tyler-Smith C, Durbin R (2016) BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data. Bioinformatics 32(11):1749–1751.  
  21. 21.
    McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20(9):1297–1303.  
  22. 22.
    Lee JH, Ang JK, Xiao X (2013) Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants. RNA 19(6):725–732.  
  23. 23.
    Pinto Y, Levanon EY (2019) Computational approaches for detection and quantification of A-to-I RNA-editing. Methods 156:25–31.  
  24. 24.
    Lin W, Piskol R, Tan MH, Li JB (2012) Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335(6074):1302; author reply 1302.  
  25. 25.
    Pickrell JK, Gilad Y, Pritchard JK (2012) Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335(6074):1302; author reply 1302.  
  26. 26.
    Kleinman CL, Majewski J (2012) Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335(6074):1302; author reply 1302.  
  27. 27.
    Piskol R, Peng Z, Wang J, Li JB (2013) Lack of evidence for existence of noncanonical RNA editing. Nat Biotechnol 31(1):19–20.  
  28. 28.
    Picardi E, Pesole G (2013) REDItools: high-throughput RNA editing detection made easy. Bioinformatics 29(14):1813–1814.  
  29. 29.
    Wang Z, Lian J, Li Q, Zhang P, Zhou Y, Zhan X, Zhang G (2016) RES-Scanner: a software package for genome-wide identification of RNA-editing sites. Gigascience 5(1):37.  
  30. 30.
    Levin JZ, Yassour M, Adiconis X, Nusbaum C, Thompson DA, Friedman N, Gnirke A, Regev A (2010) Comprehensive comparative analysis of strand-specific RNA sequencing methods. Nat Methods 7(9):709–715.  
  31. 31.
    Strom NB, Bushley KE (2016) Two genomes are better than one: history, genetics, and biotechnological applications of fungal heterokaryons. Fungal Biol Biotechnol 3:4.  
  32. 32.
    Piechotta M, Wyler E, Ohler U, Landthaler M, Dieterich C (2017) JACUSA: site-specific identification of RNA editing events from replicate sequencing data. BMC Bioinformatics 18(1):7.  
  33. 33.
    Picardi E, D’Erchia AM, Gallo A, Pesole G (2015) Detection of post-transcriptional RNA editing events. Methods Mol Biol 1269:189–205.  
  34. 34.
    Picardi E, D’Erchia AM, Montalvo A, Pesole G (2015) Using REDItools to detect RNA editing events in NGS datasets. Curr Protoc Bioinformatics 49(12.12):11–15.  
  35. 35.
    Zhang F, Lu Y, Yan S, Xing Q, Tian W (2017) SPRINT: an SNP-free toolkit for identifying RNA editing sites. Bioinformatics 33(22):3538–3548.  
  36. 36.
    John D, Weirick T, Dimmeler S, Uchida S (2017) RNAEditor: easy detection of RNA editing events and the introduction of editing islands. Brief Bioinform 18(6):993–1001.  
  37. 37.
    Cuomo CA, Guldener U, Xu JR, Trail F, Turgeon BG, Di Pietro A, Walton JD, Ma LJ, Baker SE, Rep M, Adam G, Antoniw J, Baldwin T, Calvo S, Chang YL, Decaprio D, Gale LR, Gnerre S, Goswami RS, Hammond-Kosack K, Harris LJ, Hilburn K, Kennell JC, Kroken S, Magnuson JK, Mannhaupt G, Mauceli E, Mewes HW, Mitterbauer R, Muehlbauer G, Munsterkotter M, Nelson D, O’Donnell K, Ouellet T, Qi W, Quesneville H, Roncero MI, Seong KY, Tetko IV, Urban M, Waalwijk C, Ward TJ, Yao J, Birren BW, Kistler HC (2007) The Fusarium graminearum genome reveals a link between localized polymorphism and pathogen specialization. Science 317(5843):1400–1402.  
  38. 38.
    Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Genome Project Data Processing S (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25(16):2078–2079.  
  39. 39.
    Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9(4):357–359.  
  40. 40.
    Kim D, Langmead B, Salzberg SL (2015) HISAT: a fast spliced aligner with low memory requirements. Nat Methods 12(4):357–360.  
  41. 41.
    Barnett DW, Garrison EK, Quinlan AR, Stromberg MP, Marth GT (2011) BamTools: a C++ API and toolkit for analyzing and managing BAM files. Bioinformatics 27(12):1691–1692.  
  42. 42.
    Sun Y, Li X, Wu D, Pan Q, Ji Y, Ren H, Ding K (2016) RED: A Java-MySQL software for identifying and visualizing RNA editing sites using rule-based and statistical filters. PLoS One 11(3):e0150465.  
  43. 43.
    Zhang Q (2018) Analysis of RNA editing sites from RNA-Seq data using GIREMI. Methods Mol Biol 1751:101–108.  
  44. 44.
    Xiong H, Liu D, Li Q, Lei M, Xu L, Wu L, Wang Z, Ren S, Li W, Xia M, Lu L, Lu H, Hou Y, Zhu S, Liu X, Sun Y, Wang J, Yang H, Wu K, Xu X, Lee LJ (2017) RED-ML: a novel, effective RNA editing detection method based on machine learning. Gigascience 6(5):1–8.  
  45. 45.
    Sureyya Rifaioglu A, Dogan T, Jesus Martin M, Cetin-Atalay R, Atalay V (2019) DEEPred: automated protein function prediction with multi-task feed-forward deep neural networks. Sci Rep 9(1):7344.  
  46. 46.
    Kim MS, Hur B, Kim S (2016) RDDpred: a condition-specific RNA-editing prediction model from RNA-seq data. BMC Genomics 17(Suppl 1):5.  

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2021

Authors and Affiliations

  1. 1.State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F UniversityYanglingChina
  2. 2.Department of Botany and Plant PathologyPurdue UniversityWest LafayetteUSA

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