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MicroRNA

Author(s): Behzad Hajieghrari* and Sara Rahmanian-Koshkaki

DOI: 10.2174/2211536611666220818150634

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Plant MicroRNA Potential in Targeting Sars-CoV-2 Genome Offering Efficient Antiviral MiRNA-Based Therapies

Page: [245 - 262] Pages: 18

  • * (Excluding Mailing and Handling)

Abstract

Background: In 2019, severe acute respiratory coronavirus II (or SARS-COV-2) emerged in Wuhan, China, rapidly becoming a global pandemic. Coronavirus genus (Coronaviridae) has the largest single-stranded positive-sense RNA genome (~30 kb) among the human infected single-stranded RNA viruses.

Objectives: For the study of active therapeutic plant-derived miRNA(s), it may be possible to uptake the miRNAs and their biological role in the host cell. In this study, we bioinformatically searched plant miRNAs that can potentially interact with the Sars-CoV-2 genome within the 3’- UTR region and have prompt antiviral activity.

Materials and Methods: We searched the plant miRNAs that target the 3’-UTR flanking region of the Sars-CoV-2 genome by employing the RNAHybrid, RNA22, and STarMir miRNA/target prediction tools.

Results: The RNAHybrid algorithm found 63 plant miRNAs having hybridization energy with less or equal to -25 kcal.mol-1. Besides, RNA22 and STarMir tools identified eight interactions between the plant miRNAs and the targeted RNA sequence. pvu-miR159a. 2 and sbi-miR5387b were predicted as the most effectively interacting miRNAs in targeting the 3’-UTR sequence, not only by the RNA22 tool but also by the STarMir tool at the same position. However, the GC content of the pvumiR159a. 2 is 55% instead of sbi-miR5387b, which is a GC enriched sequence (71.43%) that may activate TLR receptors.

Conclusion: In our opinion, they are potent plant-derived miRNA candidates that have a great chance of targeting the Sars-CoV-2 genome in the 3’-UTR region in vitro. Therefore, we propose pvu-miR159a.2 for studying antiviral miRNA-based therapies without any essential side effects in vivo.

Keywords: : Plant-derived miRNA, COVID-19, Sars-CoV-2, 3’-UTR, Translational repression, Antiviral miRNA-based therapy.

Graphical Abstract

[1]
Pal M, Berhanu G, Desalegn C, Kandi V. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An update. Cureus 2020; 12(3): e7423.
[http://dx.doi.org/10.7759/cureus.7423] [PMID: 32337143]
[2]
Abu-Izneid T, AlHajri N, Ibrahim AM, et al. Micro-RNAs in the regulation of immune response against SARS CoV-2 and other viral infec-tions. J Adv Res 2021; 30: 133-45.
[http://dx.doi.org/10.1016/j.jare.2020.11.013] [PMID: 33282419]
[3]
Canatan D, De Sanctis V. The impact of microRNAs (miRNAs) on the genotype of coronaviruses. Acta Biomed 2020; 91(2): 195-8.
[http://dx.doi.org/10.23750/abm.v91i2.9534] [PMID: 32420944]
[4]
Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: Synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 2010; 1803(11): 1231-43.
[http://dx.doi.org/10.1016/j.bbamcr.2010.06.013] [PMID: 20619301]
[5]
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15(8): 509-24.
[http://dx.doi.org/10.1038/nrm3838] [PMID: 25027649]
[6]
Farrokhi N, Hajieghrari B. Chronicles of dolos and apate in plant microRNAs. Biologia (Bratisl) 2020; 75(12): 2465-5.
[http://dx.doi.org/10.2478/s11756-020-00570-3]
[7]
O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne) 2018; 9: 402.
[http://dx.doi.org/10.3389/fendo.2018.00402] [PMID: 30123182]
[8]
Kehl T, Backes C, Kern F, et al. About miRNAs, miRNA seeds, target genes and target pathways. Oncotarget 2017; 8(63): 107167-75.
[http://dx.doi.org/10.18632/oncotarget.22363] [PMID: 29291020]
[9]
Trobaugh DW, Klimstra WB. MicroRNA regulation of RNA virus replication and pathogenesis. Trends Mol Med 2017; 23(1): 80-93.
[http://dx.doi.org/10.1016/j.molmed.2016.11.003] [PMID: 27989642]
[10]
Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005; 309(5740): 1577-81.
[http://dx.doi.org/10.1126/science.1113329] [PMID: 16141076]
[11]
Shimakami T, Yamane D, Jangra RK, et al. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA 2012; 109(3): 941-6.
[http://dx.doi.org/10.1073/pnas.1112263109]
[12]
Lecellier CH, Dunoyer P, Arar K, et al. A cellular microRNA mediates antiviral defense in human cells. Science 2005; 308(5721): 557-60.
[http://dx.doi.org/10.1126/science.1108784] [PMID: 15845854]
[13]
Zheng Z, Ke X, Wang M, et al. Human microRNA HSA-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome. J Virol 2013; 87(10): 5645-56.
[http://dx.doi.org/10.1128/JVI.02655-12] [PMID: 23468506]
[14]
Song L, Liu H, Gao S, Jiang W, Huang W. Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol 2010; 84(17): 8849-60.
[http://dx.doi.org/10.1128/JVI.00456-10] [PMID: 20554777]
[15]
Ingle H, Kumar S, Raut AA, et al. The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication. Sci Signal 2015; 8(406): ra126.
[http://dx.doi.org/10.1126/scisignal.aab3183] [PMID: 26645583]
[16]
Khongnomnan K, Makkoch J, Poomipak W, Poovorawan Y, Payungporn S. Human miR-3145 inhibits influenza A viruses replication by targeting and silencing viral PB1 gene. Exp Biol Med (Maywood) 2015; 240(12): 1630-9.
[http://dx.doi.org/10.1177/1535370215589051] [PMID: 26080461]
[17]
Nguyen TH, Liu X, Su ZZ, Hsu AC, Foster PS, Yang M. Potential role of microRNAs in the regulation of antiviral responses to influenza infection. Front Immunol 2018; 9: 1541.
[http://dx.doi.org/10.3389/fimmu.2018.01541] [PMID: 30022983]
[18]
Barbu MG, Condrat CE, Thompson DC, et al. MicroRNA involvement in signaling pathways during viral infection. Front Cell Dev Biol 2020; 8: 143.
[http://dx.doi.org/10.3389/fcell.2020.00143] [PMID: 32211411]
[19]
Girardi E, López P, Pfeffer S. On the importance of host microRNAs during viral infection. Front Genet 2018; 9: 439.
[http://dx.doi.org/10.3389/fgene.2018.00439] [PMID: 30333857]
[20]
Zhang L, Hou D, Chen X, et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: Evidence of cross-kingdom regula-tion by microRNA. Cell Res 2012; 22(1): 107-26.
[http://dx.doi.org/10.1038/cr.2011.158] [PMID: 21931358]
[21]
Vaucheret H, Chupeau Y. Ingested plant miRNAs regulate gene expression in animals. Cell Res 2012; 22(1): 3-5.
[http://dx.doi.org/10.1038/cr.2011.164] [PMID: 22025251]
[22]
Samad AFA, Kamaroddin MF, Sajad M. Cross-kingdom regulation by plant microRNAs provides novel insight into gene regulation. Adv Nutr 2021 Feb 1; 12(1): 197-211.
[http://dx.doi.org/10.1093/advances/nmaa095] [PMID: 32862223]
[23]
Ji L, Chen X. Regulation of small RNA stability: Methylation and beyond. Cell Res 2012; 22(4): 624-36.
[http://dx.doi.org/10.1038/cr.2012.36] [PMID: 22410795]
[24]
Liang H, Zen K, Zhang J, Zhang CY, Chen X. New roles for microRNAs in cross-species communication. RNA Biol 2013; 10(3): 367-70.
[http://dx.doi.org/10.4161/rna.23663] [PMID: 23364352]
[25]
Zhou Z, Li X, Liu J, et al. Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Res 2015; 25(1): 39-49.
[http://dx.doi.org/10.1038/cr.2014.130] [PMID: 25287280]
[26]
Wang W, Liu D, Zhang X, Chen D, Cheng Y, Shen F. Plant microRNAs in cross-kingdom regulation of gene expression. Int J Mol Sci 2018; 19(7): E2007.
[http://dx.doi.org/10.3390/ijms19072007] [PMID: 29996470]
[27]
Chin AR, Fong MY, Somlo G, et al. Cross-kingdom inhibition of breast cancer growth by plant miR159. Cell Res 2016; 26(2): 217-28.
[http://dx.doi.org/10.1038/cr.2016.13] [PMID: 26794868]
[28]
Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: An overview of nuclear functions. Int J Mol Sci 2016; 17(10): 1712.
[http://dx.doi.org/10.3390/ijms17101712] [PMID: 27754357]
[29]
Nagarajan VK, Jones CI, Newbury SF, Green PJ. XRN 5′→3′ exoribonucleases: Structure, mechanisms and functions. Biochim Biophys Acta 2013; 1829(6-7): 590-603.
[http://dx.doi.org/10.1016/j.bbagrm.2013.03.005] [PMID: 23517755]
[30]
Witkos TM, Koscianska E, Krzyzosiak WJ. Practical aspects of microRNA target prediction. Curr Mol Med 2011; 11(2): 93-109.
[http://dx.doi.org/10.2174/156652411794859250] [PMID: 21342132]
[31]
Krüger J, Rehmsmeier M. RNAhybrid: MicroRNA target prediction easy, fast and flexible. Nucleic Acids Res 2006; 34: W451-4.
[http://dx.doi.org/10.1093/nar/gkl243]
[32]
Miranda KC, Huynh T, Tay Y, et al. A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 2006; 126(6): 1203-17.
[http://dx.doi.org/10.1016/j.cell.2006.07.031] [PMID: 16990141]
[33]
Rennie W, Liu C, Carmack CS, et al. STarMir: A web server for prediction of microRNA binding sites. Nucleic Acids Res 2014; 42: W114-8.
[http://dx.doi.org/10.1093/nar/gku376] [PMID: 24803672]
[34]
Hajieghrari B, Farrokhi N, Goliaei B, Kavousi K. Computational identification of MicroRNAs and their transcript target(s) in field mustard (Brassica rapa L.). Iran J Biotechnol 2017; 15(1): 22-32.
[http://dx.doi.org/10.15171/ijb.1390] [PMID: 28959349]
[35]
Hajieghrari B, Farrokhi N, Goliaei B, Kavousi K. In silico identification of conserved miRNAs from Physcomitrella patens ESTs and their target characterization. Curr Bioinform 2019; 14(1): 33-42.
[http://dx.doi.org/10.2174/1574893612666170530081523]
[36]
Steinkraus BR, Toegel M, Fulga TA. Tiny giants of gene regulation: Experimental strategies for microRNA functional studies. Wiley Interdiscip Rev Dev Biol 2016; 5(3): 311-62.
[http://dx.doi.org/10.1002/wdev.223] [PMID: 26950183]
[37]
den Boon JA, Diaz A, Ahlquist P. Cytoplasmic viral replication complexes. Cell Host Microbe 2010; 8(1): 77-85.
[http://dx.doi.org/10.1016/j.chom.2010.06.010] [PMID: 20638644]
[38]
V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: Implications for SARS-CoV-2. Nat Rev Microbiol 2021; 19(3): 155-70.
[http://dx.doi.org/10.1038/s41579-020-00468-6] [PMID: 33116300]
[39]
van Hemert MJ, van den Worm SH, Knoops K, Mommaas AM, Gorbalenya AE, Snijder EJ. SARS-coronavirus replication/transcription complexes are membrane-protected and need a host factor for activity in vitro. PLoS Pathog 2008; 4(5): e1000054.
[http://dx.doi.org/10.1371/journal.ppat.1000054] [PMID: 18451981]
[40]
Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev 2011; 25(18): 1881-94.
[http://dx.doi.org/10.1101/gad.17352611] [PMID: 21896651]
[41]
Kincaid RP, Sullivan CS. Virus-encoded microRNAs: An overview and a look to the future. PLoS Pathog 2012; 8(12): e1003018.
[http://dx.doi.org/10.1371/journal.ppat.1003018] [PMID: 23308061]
[42]
Li X, Zou X. An overview of RNA virus-encoded microRNAs. ExRNA 2010; 1(1): 37.
[http://dx.doi.org/10.1186/s41544-019-0037-6]
[43]
Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annu Rev Microbiol 2010; 64(1): 123-41.
[http://dx.doi.org/10.1146/annurev.micro.112408.134243] [PMID: 20477536]
[44]
Duan X, Wang L, Sun G, Yan W, Yang Y. Understanding the cross-talk between host and virus in poultry from the perspectives of mi-croRNA. Poult Sci 2020; 99(4): 1838-46.
[http://dx.doi.org/10.1016/j.psj.2019.11.053] [PMID: 32241464]
[45]
Umbach JL, Cullen BR. The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev 2009; 23(10): 1151-64.
[http://dx.doi.org/10.1101/gad.1793309] [PMID: 19451215]
[46]
Bruscella P, Bottini S, Baudesson C, Pawlotsky JM, Feray C, Trabucchi M. Viruses and miRNAs: More Friends than Foes. Front Microbiol 2017; 8: 824.
[http://dx.doi.org/10.3389/fmicb.2017.00824] [PMID: 28555130]
[47]
Ojha CR, Rodriguez M, Dever SM, Mukhopadhyay R, El-Hage N. Mammalian microRNA: An important modulator of host-pathogen inter-actions in human viral infections. J Biomed Sci 2016; 23(1): 74.
[http://dx.doi.org/10.1186/s12929-016-0292-x] [PMID: 27784307]
[48]
Bernier A, Sagan SM. The diverse roles of microRNAs at the host−virus interface. Viruses 2018; 10(8): 440.
[http://dx.doi.org/10.3390/v10080440] [PMID: 30126238]
[49]
Mahajan VS, Drake A, Chen J. Virus-specific host miRNAs: Antiviral defenses or promoters of persistent infection? Trends Immunol 2009; 30(1): 1-7.
[http://dx.doi.org/10.1016/j.it.2008.08.009] [PMID: 19059006]
[50]
Russo A, Potenza N. Antiviral effects of human microRNAs and conservation of their target sites. FEBS Lett 2011; 585(16): 2551-5.
[http://dx.doi.org/10.1016/j.febslet.2011.07.015] [PMID: 21784072]
[51]
Gottwein E, Cullen BR. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 2008; 3(6): 375-87.
[http://dx.doi.org/10.1016/j.chom.2008.05.002] [PMID: 18541214]
[52]
Hum C, Loiselle J, Ahmed N, Shaw TA, Toudic C, Pezacki JP. MicroRNA mimics or inhibitors as antiviral therapeutic approaches against COVID-19. Drugs 2021; 81(5): 517-31.
[http://dx.doi.org/10.1007/s40265-021-01474-5] [PMID: 33638807]
[53]
Alvarez JP, Pekker I, Goldshmidt A, Blum E, Amsellem Z, Eshed Y. Endogenous and synthetic microRNAs stimulate simultaneous, effi-cient, and localized regulation of multiple targets in diverse species. Plant Cell 2006; 18(5): 1134-51.
[http://dx.doi.org/10.1105/tpc.105.040725] [PMID: 16603651]
[54]
Schwab R, Ossowski S, Riester M, Warthmann N, Weigel D. Highly specific gene silencing by artificial microRNAs in Arabidopsis. Plant Cell 2006; 18(5): 1121-33.
[http://dx.doi.org/10.1105/tpc.105.039834] [PMID: 16531494]
[55]
Nielsen CB, Shomron N, Sandberg R, Hornstein E, Kitzman J, Burge CB. Determinants of targeting by endogenous and exogenous mi-croRNAs and siRNAs. RNA 2007; 13(11): 1894-910.
[http://dx.doi.org/10.1261/rna.768207] [PMID: 17872505]
[56]
Poulin F, Sonenberg N. Mechanism of Translation Initiation in Eukaryotes. In: Madame Curie Bioscience Database Austin (TX): Landes Bioscience;. 2000-13.
[57]
Cencic R, Desforges M, Hall DR, et al. Blocking eIF4E-eIF4G interaction as a strategy to impair coronavirus replication. J Virol 2011; 85(13): 6381-9.
[http://dx.doi.org/10.1128/JVI.00078-11] [PMID: 21507972]
[58]
Mlotshwa S, Pruss GJ, MacArthur JL, et al. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res 2015; 25(4): 521-4.
[http://dx.doi.org/10.1038/cr.2015.25] [PMID: 25721325]
[59]
Li Z, Xu R, Li N. MicroRNAs from plants to animals, do they define a new messenger for communication? Nutr Metab (Lond) 2018; 15(1): 68.
[http://dx.doi.org/10.1186/s12986-018-0305-8] [PMID: 30302122]
[60]
Dávalos A, Pinilla L, López de Las Hazas MC, et al. Dietary microRNAs and cancer: A new therapeutic approach? Semin Cancer Biol 2021; 73: 19-29.
[http://dx.doi.org/10.1016/j.semcancer.2020.10.006] [PMID: 33086083]
[61]
Zhang L, Zheng Y, Jagadeeswaran G, Li Y, Gowdu K, Sunkar R. Identification and temporal expression analysis of conserved and novel microRNAs in Sorghum. Genomics 2011; 98(6): 460-8.
[http://dx.doi.org/10.1016/j.ygeno.2011.08.005] [PMID: 21907786]
[62]
Akpinar BA, Budak H. Dissecting miRNAs in wheat D genome progenitor, Aegilops tauschii. Front Plant Sci 2016; 7: 606.
[http://dx.doi.org/10.3389/fpls.2016.00606] [PMID: 27200073]
[63]
Hajieghrari B, Farrokhi N. Investigation on the conserved microRNA genes in higher plants. Plant Mol Biol Report 2021; 39(1): 10-23.
[http://dx.doi.org/10.1007/s11105-020-01228-9]
[64]
Millar AA, Lohe A, Wong G. Biology and function of miR159 in plants. Plants 2019; 8(8): 255.
[http://dx.doi.org/10.3390/plants8080255] [PMID: 31366066]
[65]
Contreras-Cubas C, Rabanal FA, Arenas-Huertero C, Ortiz MA, Covarrubias AA, Reyes JL. The Phaseolus vulgaris miR159a precursor encodes a second differentially expressed microRNA. Plant Mol Biol 2012; 80(1): 103-15.
[http://dx.doi.org/10.1007/s11103-011-9847-0] [PMID: 22083131]
[66]
Zhao Y, Mo B, Chen X. Mechanisms that impact microRNA stability in plants. RNA Biol 2012; 9(10): 1218-23.
[http://dx.doi.org/10.4161/rna.22034] [PMID: 22995833]