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In silico analysis of endogenous siRNAs associated transposable elements and NATs in Schistosoma japonicum reveals their putative roles during reproductive development

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Abstract

Schistosomiasis is a neglected tropical disease caused by trematode of the genus Schistosoma. Successful reproductive development is critical for the production of eggs, which are responsible for host pathology and disease dissemination. Endogenous small non-coding RNAs play important roles in many biological processes such as protection against foreign pathogens, cell differentiation, and chromosomal stability by regulating target gene expression at the transcriptional and post-transcriptional levels. In this study, we performed in silico analysis of endogenous small non-coding RNAs in different stages, and sex of S. japonicum focusing on endogenous small interfering RNAs (endo-siRNAs) generated from transposable elements (TEs) and natural antisense transcripts (NATs). Both total and unique siRNA populations show 18–30 nt in length, but the predominant size was 20 nt and the leading first base was adenosine. Sense TE-derived endo-siRNAs reads were higher than antisense reads at different relative positions of TEs, whereas no such difference was observed for NAT-derived endo-siRNAs. TE- and NAT-derived endo-siRNAs were more enriched in the male compared to female worms, with the higher relative expression in early phase of pairing. Putative targets of endo-siRNAs indicated more of them in males (106 and 66) than in females (6 and 23) for TE- and NAT-derived endo-siRNAs, respectively. Our preliminary study revealed vital role of endo-siRNAs during the reproductive development of S. japonicum and provide clues for putative novel targets to suppress worm reproduction and direction for effective anti-schistosomal drug development.

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References

  • Beckmann S, Quack T, Burmeister C, Buro C, Long T, Dissous C, Grevelding CG (2010) Schistosoma mansoni: signal transduction processes during the development of the reproductive organs. Parasitology 137(3):497–520

    Article  CAS  PubMed  Google Scholar 

  • Benson G (1999) Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res 27(2):573–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biryukova I, Ye T (2015) Endogenous siRNAs and piRNAs derived from transposable elements and genes in the malaria vector mosquito Anopheles gambiae. BMC Genomics 16:278

    Article  PubMed  PubMed Central  Google Scholar 

  • Boros DL (1989) Immunopathology of Schistosoma mansoni infection. Clin Microbiol Rev 2(3):250–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai P, Hou N, Piao X, Liu S, Liu H, Yang F, Wang J, Jin Q, Wang H, Chen Q (2011) Profiles of small non-coding RNAs in Schistosoma japonicum during development. PLoS Negl Trop Dis 5(8):e1256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai P, Piao X, Hao L, Liu S, Hou N, Wang H, Chen Q (2013) A deep analysis of the small non-coding RNA population in Schistosoma japonicum eggs. PLoS One 8(5):e64003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Claycomb JM (2014) Ancient endo-siRNA pathways reveal new tricks. Curr Biol 24(15):R703–15

  • Cerutti H, Casas-Mollano JA (2006) On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet 50(2):81–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebersberger I, Knobloch J, Kunz W (2005) Cracks in the shell--zooming in on eggshell formation in the human parasite Schistosoma mansoni. Dev Genes Evol 215(5):261–267

    Article  PubMed  Google Scholar 

  • Fu L, Niu B, Zhu Z, Wu S, Li W (2012) CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28(23):3150–3152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghildiyal M, Seitz H, Horwich MD, Li C, Du T, Lee S, Xu J, Kittler EL, Zapp ML, Weng Z, Zamore PD (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320(5879):1077–1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33:D121–D124

    Article  CAS  PubMed  Google Scholar 

  • Hao L, Cai P, Jiang N, Wang H, Chen Q (2010) Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum. BMC Genomics 11:55

    Article  PubMed  PubMed Central  Google Scholar 

  • Hoffmann KF, Wynn TA, Dunne DW (2002) Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control and immunopathology. Adv Parasitol 52:265–307

    Article  PubMed  Google Scholar 

  • Kapitonov VV, Jurka J (2003) Molecular paleontology of transposable elements in the Drosophila melanogaster genome. Proc Natl Acad Sci 100(11):6569–6574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap C, Suzuki M, Kawai J (2005) Antisense transcription in the mammalian transcriptome. Science 309(5740):1564–1566

    Article  PubMed  Google Scholar 

  • Katiyar-Agarwal S, Jin H (2010) Role of small RNAs in host-microbe interactions. Annu Rev Phytopathol 48:225–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawamura Y, Saito K, Kin T, Ono Y, Asai K, Sunohara T, Okada TN, Siomi MC, Siomi H (2008) Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 453(7196):793–797

    Article  CAS  PubMed  Google Scholar 

  • Kim VN (2005) Small RNAs: classification, biogenesis, and function. Molecules and cells 19(1):1–15

    CAS  PubMed  Google Scholar 

  • Kunz W (2001) Schistosome male-female interaction: induction of germ-cell differentiation. Trends Parasitol 17(5):227–231

    Article  CAS  PubMed  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson J, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie W, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J, International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    Article  CAS  PubMed  Google Scholar 

  • Langmead B (2010) Aligning short sequencing reads with Bowtie. Curr Protoc Bioinformatics Chapter:Unit-11.7

  • Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10(3):R25

    Article  PubMed  PubMed Central  Google Scholar 

  • Li YY, Qin L, Guo ZM, Liu L, Xu H, Hao P, Su J, Shi Y, He WZ, Li YX (2006) In silico discovery of human natural antisense transcripts. BMC Bioinformatics 7:18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okamura K, Balla S, Martin R, Liu N, Lai EC (2008a) Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster. Nat Struct Mol Biol 15(6):581–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okamura K, Chung WJ, Ruby JG, Guo H, Bartel DP, Lai EC (2008b) The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 453(7196):803–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Popiel I (1986) Male-stimulated female maturation inSchistosoma: a review. J Chem Ecol 12(8):1745–1754

    Article  CAS  PubMed  Google Scholar 

  • Rebollo R, Zhang Y, Mager DL (2012) Transposable elements: not as quiet as a mouse. Genome Biol 13(6):159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabalina SA, Koonin EV (2008) Origins and evolution of eukaryotic RNA interference. Trends Ecol Evol 23(10):578–587

    Article  PubMed  PubMed Central  Google Scholar 

  • Sobreira TJ, Durham AM, Gruber A (2006) TRAP: automated classification, quantification and annotation of tandemly repeated sequences. Bioinformatics 22(3):361–362

    Article  CAS  PubMed  Google Scholar 

  • Soumillon M, Necsulea A, Weier M, Brawand D, Zhang X, Gu H, Barthes P, Kokkinaki M, Nef S, Gnirke A, Dym M, de Massy B, Mikkelsen TS, Kaessmann H (2013) Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Rep 3(6):2179–2190

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Wang SW, Li C, Hu W, Ren YJ, Wang JQ (2014) Transcriptome profilings of female Schistosoma japonicum reveal significant differential expression of genes after pairing. Parasitol Res 113(3):881–892

    Article  PubMed  Google Scholar 

  • Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20(5):515–524

    Article  CAS  PubMed  Google Scholar 

  • Vazquez F (2006) Arabidopsis endogenous small RNAs: highways and byways. Trends Plant Sci 11(9):460–468

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Czech B, Crunk A, Wallace A, Mitreva M, Hannon GJ, Davis RE (2011) Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Res 21(9):1462–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Yu Y, Shen H, Qing T, Zheng Y, Li Q, Mo X, Wang S, Li N, Chai R, Xu B, Liu M, Brindley PJ, McManus DP, Feng Z, Shi L, Hu W (2017) Dynamic transcriptomes identify biogenic amines and insect-like hormonal regulation for mediating reproduction in Schistosoma japonicum. Nat Commun 8:14693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453(7194):539–543

    Article  CAS  PubMed  Google Scholar 

  • Werner A, Carlile M, Swan D (2009) What do natural antisense transcripts regulate? RNA Biol 6(1):43–48

    Article  CAS  PubMed  Google Scholar 

  • Werner A, Cockell S, Falconer J, Carlile M, Alnumeir S, Robinson J (2014) Contribution of natural antisense transcription to an endogenous siRNA signature in human cells. BMC Genomics 15:19

    Article  PubMed  PubMed Central  Google Scholar 

  • WHO (2017) Schistosomiasis, fact sheet No. 115. Updated October. http://www.who.int/mediacentre/factsheets/fs115/en/

  • Zhang X, Xia J, Lii YE, Barrera-Figueroa BE, Zhou X, Gao S, Lu L, Niu D, Chen Z, Leung C, Wong T, Zhang H, Guo J, Li Y, Liu R, Liang W, Zhu J-K, Zhang W, Jin H (2012) Genome-wide analysis of plant nat-siRNAs reveals insights into their distribution, biogenesis and function. Genome Biol 13(3):R20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Zheng H, Chen Y, Zhang L, Wang K, Guo J, Huang Z, Zhang B, Huang W, Jin K, Dou T, Hasegawa M, Wang L, Zhang Y, Zhou J, Tao L, Cao Z, Li Y, Vinar T, Brejova B, Brown D, Li M, Miller DJ, Blair D, Zhong Y, Chen Z, Liu F, Hu W, Wang ZQ, Zhang QH, Song HD, Chen S, Xu X, Xu B, Ju C, Huang Y, Brindley PJ, McManus DP, Feng Z, Han ZG, Lu G, Ren S, Wang Y, Gu W, Kang H, Chen J, Chen X, Chen S, Wang L, Yan J, Wang B, Lv X, Jin L, Wang B, Pu S, Zhang X, Zhang W, Hu Q, Zhu G, Wang J, Yu J, Wang J, Yang H, Ning Z, Beriman M, Wei CL, Ruan Y, Zhao G, Wang S, Liu F, Zhou Y, Wang ZQ, Lu G, Zheng H, Brindley PJ, McManus DP, Blair D, Zhang QH, Zhong Y, Wang S, Han ZG, Chen Z, Wang S, Han ZG, Chen Z (2009) The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460(7253):345–351

    Article  CAS  PubMed Central  Google Scholar 

  • Zhu L, Zhao J, Wang J, Hu C, Peng J, Luo R, Zhou C, Liu J, Lin J, Jin Y, Davis RE, Cheng G (2016) MicroRNAs are involved in the regulation of ovary development in the pathogenic blood fluke Schistosoma japonicum. PLoS Pathog 12(2):e1005423

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by National Natural Science Foundation of China (31472187 and 31672550), National Key Research and Development Program of China (2017YFD0501300), and The Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences.

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  1. Bikash Ranjan Giri and Jiannan Ye contributed equally to this work.

Authors and Affiliations

  1. Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, 200241, China

    Bikash Ranjan Giri, Yongjun Chen & Guofeng Cheng

  2. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China

    Jiannan Ye & Chaochun Wei

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  1. Bikash Ranjan Giri
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  2. Jiannan Ye
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Correspondence to Chaochun Wei or Guofeng Cheng.

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Electronic supplementary material

Fig. S1.

Pipeline for identification of novel endo-siRNA in S. japonicum. (PPTX 77 kb)

Fig. S2.

Characteristic length and first base distribution of unique endo-siRNA from different libraries. Female: mixed female worm pool; Male: mixed male worm pool. (PPTX 479 kb)

Table S1

(PPTX 31 kb)

Table S2

(PPTX 31 kb)

Data S1

This data file contains mRNA sources of NAT-derived endo-siRNAs. (XLSX 11 kb)

Data S2

This data file contains the top 50 TE-derived male- and female-enriched endo-siRNAs. (XLSX 34 kb)

Data S3

This data file contains the top 50 NAT-derived male and female-enriched endo-siRNAs. (XLSX 30 kb)

Data S4

This data file contains target mRNAs for the 50 TE- and NAT-derived sex-enriched endo-siRNAs. (XLSX 29 kb)

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Giri, B.R., Ye, J., Chen, Y. et al. In silico analysis of endogenous siRNAs associated transposable elements and NATs in Schistosoma japonicum reveals their putative roles during reproductive development. Parasitol Res 117, 1549–1558 (2018). https://doi.org/10.1007/s00436-018-5830-x

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