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Computational identification of novel microRNAs and their targets in the malarial vector, Anopheles stephensi

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Systems and Synthetic Biology

Abstract

MicroRNAs are a ~22 nucleotide small non-coding RNAs found in animals, plants and viruses. They regulate key cellular processes by enhancing, degrading or silencing protein coding targets. Currently most of the data on miRNA is available from Drosophila . Given their important post-transcriptional role in several organisms, there is a need to understand the miRNA mediated processes in normal and abnormal conditions. Here we report four novel microRNAs ast - mir - 2502, ast - mir - 2559, ast - mir - 3868 and ast - mir - 9891 in Anopheles stephensi identified from a set of 3,052 transcriptome sequences, showing average minimum free energy of −31.8 kcal/mol of duplex formation with mRNA indicating their functional relevance. Phylogenetic study shows conservation of sequence signatures within the Class Insecta. Furthermore, 26 potential targets of these four miRNAs have been predicted that play an important role in the mosquito life-cycle. This work leads to novel leads and experimental possibilities for improved understanding of gene regulatory processes in mosquito.

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References

  • Abdalla H, Wilding CS, Nardini L, Pignatelli P, Koekemoer L, Ranson H, Coetzee M (2014) Insecticide resistance in Anopheles arabiensis in Sudan: temporal trends and underlying mechanisms. Parasit Vectors 7:213. doi:10.1186/1756-3305-7-213

    Article  PubMed Central  PubMed  Google Scholar 

  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bartel D (2004) MicroRNAs: genomics, biogenesis, mechanism and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  • Bartel D (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bennett V, Chen L (2001) Ankyrins and cellular targeting of diverse membrane proteins to physiological sites. Curr Opin Cell Biol 13(1):61–67

    Article  CAS  PubMed  Google Scholar 

  • Dasso M (1993) RCC1 in the cell cycle: the regulator of chromosome condensation takes on new roles. Trends Biochem Sci 18(3):96–101

    Article  CAS  PubMed  Google Scholar 

  • Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the microprocessor complex. Nature 432:231–235

    Article  CAS  PubMed  Google Scholar 

  • El-Assaad F, Hempel C et al (2011) Differential microRNA expression in experimental cerebral and non-cerebral malaria. Infect Immun 79(6):2379–2384

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106(1):23–34

    Article  CAS  PubMed  Google Scholar 

  • Grüring C, Heiber A, Kruse F, Ungefehr J, Gilberger TW, Spielmann T (2011) Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions. Nat Commun 2:165. doi:10.1038/ncomms1169

    Article  PubMed  Google Scholar 

  • Guan X, Middlebrooks BW, Alexander S, Wasserman SA (2006) Mutation of TweedleD, a member of an unconventional cuticle protein family, alters body shape in Drosophila. Proc Natl Acad Sci USA 103:16794–16799

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  PubMed  Google Scholar 

  • Hittinger CT, Johnston M, Tossberg JT, Rokas A (2010) Leveraging skewed transcript abundance by RNA-Seq to increase the genomic depth of the tree of life. PNAS 107(4):1476–1481. doi:10.1073/pnas.0910449107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Joazeiro CA, Weissman AM (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102(5):549–552

    Article  CAS  PubMed  Google Scholar 

  • Kariu T, Yuda M, Yano K, Chinzei Y (2002) MAEBL is essential for malarial sporozoite infection of the mosquito salivary gland. J Exp Med 195(10):1317–1323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115(2):209–216

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Imoto S, Miyano S (2003) Inferring gene networks from time series microarray data using dynamic Bayesian networks. Brief Bioinform 4(3):228–235

    Article  CAS  PubMed  Google Scholar 

  • Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acid Research 42:D68–D73

    Article  CAS  Google Scholar 

  • La Monte G, Philip N, Reardon J et al (2012) Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance. Cell Host Microbe 12(2):187–199

    Article  Google Scholar 

  • Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11(1):39–46

    Article  CAS  PubMed  Google Scholar 

  • Mead EA, Tu Z (2008) Cloning, characterization, and expression of microRNAs from the Asian malaria mosquito, Anopheles stephensi. BMC Genomics 9:244

    Article  PubMed Central  PubMed  Google Scholar 

  • Megy K et al (2012) VectorBase: improvements to a bioinformatics resource for invertebrate vector genomics. Nucleic Acids Res 40:D729–D734

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Miller LH, Baruch DI, Marsh K, Doumbo OK (2002) The pathogenic basis of malaria. Nature 415:673–679. doi:10.1038/415673a

    Article  CAS  PubMed  Google Scholar 

  • Nwane P, Etang J, ChouaÏbou M, Toto JC, Koffi A, Mimpfoundi R, Simard F (2014) Multiple insecticide resistance mechanisms in Anopheles gambiae s.l. populations from Cameroon, Central Africa. Parasit Vectors 6:41. doi:10.1186/1756-3305-6-41

    Article  Google Scholar 

  • Ocampo M, Curtidor H, Vera R, Valbuena JJ, Rodríguez LE, Puentes A, López R, García JE, Tovar D, Pacheco P, Navarro MA, Patarroyo ME (2004) MAEBL Plasmodium falciparum protein peptides bind specifically to erythrocytes and inhibit in vitro merozoite invasion. Biochem Biophys Res Commun 315(2):319–329

    Article  CAS  PubMed  Google Scholar 

  • Rathjen T, Nicol C, Mcconkey G, Dalmay T (2006) Analysis of short RNAs in the malaria parasite and its red blood cell host. FEBS Lett. doi:10.1016/j.febslet.2006.08.063

    Google Scholar 

  • Rubtsov AM, Lopina OD (2000) Ankyrins. FEBS lett 482(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Schlöndorff J, Blobel CP (1999) Metalloprotease–disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 112:3603–3617

    PubMed  Google Scholar 

  • Schwarz SD, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115(2):199–208

    Article  CAS  PubMed  Google Scholar 

  • Sinka ME et al (2011) The dominant Anopheles vectors of human malaria in Asia-Pacific: occurrence data, distribution maps and bionomic précis. Parasit Vectors 4:89. doi:10.1186/1756-3305-4-89

    Article  PubMed Central  PubMed  Google Scholar 

  • Stefan HIK, Amy RN, Tresa SF, Peter B, John HA (1998) A family of chimeric erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci 95:1230–1235

    Article  Google Scholar 

  • Sturm A, Amino R, van de Sand C et al (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313(5791):1287–1290. doi:10.1126/science.1129720

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tikar SN, Mendki MJ, Sharma AK, Sukumaran D, Veer V, Prakash S, Parashar BD (2011) Resistance status of the malaria vector mosquitoes, Anopheles stephensi and Anopheles subpictus towards adulticides and larvicides in arid ad semi-arid areas of India. J Insect Sci 11:1–10

    Article  Google Scholar 

  • Xu T, Zhong D, Tang L, Chang X, Fu F, Yan G, Zheng B (2014) Anopheles sinensis mosquito insecticide resistance: comparison of three mosquito sample collection and preparation methods and mosquito age in resistance measurements. Parasit Vectors 7:54. doi:10.1186/1756-3305-7-54

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xue C, Li F, He T, Liu GP, Li Y, Zhang X (2005) Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine. BMC Bioinform 6:310. doi:10.1186/1471-2105-6-310

    Article  Google Scholar 

  • Zeng Y, Cullen BR (2004) Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32(16):4776–4785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W (2004) Single processing center models for human Dicer and bacterial RNase III. Cell 118(1):57–68

    Article  CAS  PubMed  Google Scholar 

  • Zhao X, Smartt CT, Hillyer JF, Christensen BM (2000) A novel member of the RING-finger gene family associated with reproductive tissues of the mosquito, Aaedes aegypti. Insect Mol Biol 9(3):301–308

    Article  CAS  PubMed  Google Scholar 

  • Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31(13):3406–3415

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the State Inter-University Center for Excellence in Bioinformatics, University of Kerala for providing the infrastructure and funds for carrying out the computation involved in the work.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Computational Biology and Bioinformatics, University of Kerala, Trivandrum, Kerala, India

    Remya Krishnan, Vinod Kumar, Achuthsankar S. Nair & Pawan K. Dhar

  2. Synthetic Biology Group, Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, U.P., India

    Vivek Ananth, Shailja Singh & Pawan K. Dhar

  3. Department of Parasitology and Mycology, Institut Pasteur, Paris, France

    Shailja Singh

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  1. Remya Krishnan
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  2. Vinod Kumar
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  3. Vivek Ananth
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  5. Achuthsankar S. Nair
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Correspondence to Pawan K. Dhar.

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Krishnan, R., Kumar, V., Ananth, V. et al. Computational identification of novel microRNAs and their targets in the malarial vector, Anopheles stephensi . Syst Synth Biol 9, 11–17 (2015). https://doi.org/10.1007/s11693-014-9159-1

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  • DOI: https://doi.org/10.1007/s11693-014-9159-1

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