Abstract
Antisense RNA molecule represents a unique type of DNA transcript that comprises 19–23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.
中文概要
该综述较为全面地概述了当前反义RNA 的研究现状,特别是它的形成模式以及参与调节目的基因的调节机制。同时,还概述了反义RNA在病毒和癌症治疗以及在遗传改造植物和微生物中 的应用,为拟计划开展反义RNA 研究的学者提 供了指导。
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References
Adams L, 2017. Non-coding RNA: pri-miRNA processing: structure is key. Nat Rev Genet, 18(3):145. https://doi.org/10.1038/nrg.2017.6
Aida R, Kishimoto S, Tanaka Y, et al., 2000. Modification of flower color in torenia (Torenia fournieri Lind.) by genetic transformation. Plant Sci, 153(1):33–42. https://doi.org/10.1016/S0168-9452(99)00239-3
Appasani K, 2004. RNA interference technology in drug validation and development: RNomics approach. Pharmacogenomics, 5(1):19–23. https://doi.org/10.1517/phgs.5.1.19.25680
Boland CR, 2017. Non-coding RNA: it’s not junk. Dig Dis Sci, 62(5):1107–1109. https://doi.org/10.1007/s10620-017-4506-1
Bustin SA, Murphy J, 2013. RNA biomarkers in colorectal cancer. Methods, 59(1):116–125. https://doi.org/10.1016/j.ymeth.2012.10.003
Cavalli F, 2013. An appeal to world leaders: stop cancer now. Lancet, 381(9865):425–426. https://doi.org/10.1016/S0140-6736(13)60059-8
Creasey KM, Zhai JX, Borges F, et al., 2014. miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis. Nature, 508(7496):411–415. https://doi.org/10.1038/nature13069
Cullen BR, 2014. Viruses and RNA interference: issues and controversies. J Virol, 88(22):12934–12936. https://doi.org/10.1128/Jvi.01179-14
Day AG, Bejarano ER, Buck KW, et al., 1991. Expression of an antisense viral gene in transgenic tobacco confers resistance to the DNA virus tomato golden mosaic virus. Proc Natl Acad Sci USA, 88(15):6721–6725. https://doi.org/10.1073/pnas.88.15.6721
Dodo HW, Konan KN, Chen FC, et al., 2008. Alleviating peanut allergy using genetic engineering: the silencing of the immunodominant allergen Ara h 2 leads to its significant reduction and a decrease in peanut allergenicity. Plant Biotechnol J, 6(2):135–145. https://doi.org/10.1111/j.1467-7652.2007.00292.x
García-Rico RO, Martín JF, Fierro F, 2007. The pga1 gene of Penicillium chrysogenum NRRL 1951 encodes a heterotrimeric G protein alpha subunit that controls growth and development. Res Microbiol, 158(5):437–446. https://doi.org/10.1016/j.resmic.2007.03.001
Ge Q, McManus MT, Nguyen T, et al., 2003. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci USA, 100(5): 2718–2723. https://doi.org/10.1073/pnas.0437841100
Haase AD, Fenoglio S, Muerdter F, et al., 2010. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev, 24(22):2499–2504. https://doi.org/10.1101/Gad.1968110
Hansen PL, Hjertholm P, Vedsted P, 2015. Increased diagnostic activity in general practice during the year preceding colorectal cancer diagnosis. Int J Cancer, 137(3): 615–624. https://doi.org/10.1002/ijc.29418
Iorio MV, Ferracin M, Liu CG, et al., 2005. MicroRNA gene expression deregulation in human breast cancer. Cancer Res, 65(16):7065–7070. https://doi.org/10.1158/0008-5472.CAN-05-1783
Jacob F, Monod J, 1961. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol, 3(3):318–356. https://doi.org/10.1016/S0022-2836(61)80072-7
Ji YD, Lei T, 2013. Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria. Sci Prog, 96(1):43–60. https://doi.org/10.3184/003685013X13617194309028
Khani MH, Yeganeh F, Sotoodehnejadnematalahi F, 2016. Long non-coding RNAs; new perspective for autoimmune disease. MOJ Immunol, 3(3):00090. https://doi.org/10.15406/moji.2016.03.00090
Kim J, Chang C, Tucker ML, 2015. To grow old: regulatory role of ethylene and jasmonic acid in senescence. Front Plant Sci, 6:20. https://doi.org/10.3389/Fpls.2015.00020
Kim YK, Kim B, Kim VN, 2016. Re-evaluation of the roles of DROSHA, Exportin 5, and DICER in microRNA biogenesis. Proc Natl Acad Sci USA, 113(13):E1881–E1889. https://doi.org/10.1073/pnas.1602532113
Koch L, 2014. Population genomics: a new window into the genetics of complex diseases. Nat Rev Genet, 15(10): 644–645. https://doi.org/10.1038/nrg3815
Lam JKW, Chow MYT, Zhang Y, et al., 2015. siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids, 4(9):e252. https://doi.org/10.1038/mtna.2015.23
Lau NC, Lim LP, Weinstein EG, et al., 2001. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 294(5543):858–862. https://doi.org/10.1126/science.1065062
Lee RC, Feinbaum RL, Ambros V, 1993. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75(5):843–854. https://doi.org/10.1016/0092-8674(93)90529-Y
Legeai F, Derrien T, 2015. Identification of long non-coding RNAs in insects genomes. Curr Opin Insect Sci, 7:37–44. https://doi.org/10.1016/j.cois.2015.01.003
Ling H, Fabbri M, Calin GA, 2013. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov, 12(11):847–865. https://doi.org/10.1038/nrd4140
Lu XB, Yu Q, Binder GK, et al., 2004. Antisense-mediated inhibition of human immunodeficiency virus (HIV) replication by use of an HIV type 1-based vector results in severely attenuated mutants incapable of developing resistance. J Virol, 78(13):7079–7088. https://doi.org/10.1128/Jvi.78.13.7079-7088.2004
Luckanagul JA, Lee LA, You SJ, et al., 2015. Plant virus incorporated hydrogels as scaffolds for tissue engineering possess low immunogenicity in vivo. J Biomed Mater Res A, 103(3):887–895. https://doi.org/10.1002/jbm.a.35227
Mattick JS, 2009. The genetic signatures of noncoding RNAs. PLoS Genet, 5(4):e1000459. https://doi.org/10.1371/journal.pgen.1000459
Mohr AM, Mott JL, 2015. Overview of microRNA biology. Semin Liver Dis, 35(1):3–11. https://doi.org/10.1055/s-0034-1397344
Moralejo FJ, Cardoza RE, Gutierrez S, et al., 2002. Silencing of the aspergillopepsin B (pepB) gene of Aspergillus awamori by antisense RNA expression or protease removal by gene disruption results in a large increase in thaumatin production. Appl Environ Microbiol, 68(7): 3550–3559. https://doi.org/10.1128/AEM.68.7.3550-3559.2002
Mourier T, 2011. Retrotransposon-centered analysis of piRNA targeting shows a shift from active to passive retrotransposon transcription in developing mouse testes. BMC Genomics, 12:440. https://doi.org/10.1186/1471-2164-12-440
Nishida KM, Iwasaki YW, Murota Y, et al., 2015. Respective functions of two distinct Siwi complexes assembled during PIWI-interacting RNA biogenesis in Bombyx germ cells. Cell Rep, 10(2):193–203. https://doi.org/10.1016/j.celrep.2014.12.013
Nishimura T, Fabian MR, 2016. Scanning for a unified model for translational repression by microRNAs. EMBO J, 35(11):1158–1159. https://doi.org/10.15252/embj.201694324
Nizampatnam NR, Kumar VD, 2011. Intron hairpin and transitive RNAi mediated silencing of orfH522 transcripts restores male fertility in transgenic male sterile tobacco plants expressing orfH522. Plant Mol Biol, 76(6):557–573. https://doi.org/10.1007/s11103-011-9789-6
Oeller PW, Lu MW, Taylor LP, et al., 1991. Reversible inhibition of tomato fruit senescence by antisense RNA. Science, 254(5030):437–439. https://doi.org/10.1126/science.1925603
Patil SD, Sharma R, Srivastava S, et al., 2013. Downregulation of yidC in Escherichia coli by antisense RNA expression results in sensitization to antibacterial essential oils eugenol and carvacrol. PLoS ONE, 8(3):e57370. https://doi.org/10.1371/journal.pone.0057370
Qi P, Du X, 2013. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol, 26(2): 155–165. https://doi.org/10.1038/modpathol.2012.160
Rajan KS, Ramasamy S, 2014. Retrotransposons and piRNA: the missing link in central nervous system. Neurochem Int, 77:94–102. https://doi.org/10.1016/j.neuint.2014.05.017
Riley KJ, Yario TA, Steitz JA, 2012. Association of Argonaute proteins and microRNAs can occur after cell lysis. RNA, 18(9):1581–1585. https://doi.org/10.1261/rna.034934.112
Ross RJ, Weiner MM, Lin HF, 2014. PIWI proteins and PIWI-interacting RNAs in the soma. Nature, 505(7483): 353–359. https://doi.org/10.1038/nature12987
Rusk N, 2015. Understanding noncoding RNAs. Nat Methods, 12(1):35. https://doi.org/10.1038/nmeth.3235
Salehuzzaman SNIM, Jacobsen E, Visser RGF, 1993. Isolation and characterization of a cDNA encoding granule-bound starch synthase in cassava (Manihot esculenta Crantz) and its antisense expression in potato. Plant Mol Biol, 23(5):947–962. https://doi.org/10.1007/Bf00021811
Salomon R, Webster RG, 2009. The influenza virus enigma. Cell, 136(3):402–410. https://doi.org/10.1016/j.cell.2009.01.029
Sandhu APS, Abdelnoor RV, Mackenzie SA, 2007. Transgenic induction of mitochondrial rearrangements for cytoplasmic male sterility in crop plants. Proc Natl Acad Sci USA, 104(6):1766–1770. https://doi.org/10.1073/pnas.0609344104
Saurabh S, Vidyarthi AS, Prasad D, 2014. RNA interference: concept to reality in crop improvement. Planta, 239(3): 543–564. https://doi.org/10.1007/s00425-013-2019-5
Schmidt FR, 2009. The RNA interference—virus interplay: tools of nature for gene modulation, morphogenesis, evolution and a possible mean for aflatoxin control. Appl Microbiol Biotechnol, 83(4):611–615. https://doi.org/10.1007/s00253-009-2007-7
Schmiedel JM, Klemm SL, Zheng YN, et al., 2015. MicroRNA control of protein expression noise. Science, 348(6230): 128–132. https://doi.org/10.1126/science.aaa1738
Simons RW, Hoopes BC, McClure WR, et al., 1983. Three promoters near the termini of IS10: pIN, pOUT, and pIII. Cell, 34(2):673–682. https://doi.org/10.1016/0092-8674(83)90400-2
Szafranski P, Mello CM, Sano T, et al., 1997. A new approach for containment of microorganisms: dual control of streptavidin expression by antisense RNA and the T7 transcription system. Proc Natl Acad Sci USA, 94(4): 1059–1063. https://doi.org/10.1073/pnas.94.4.1059
Tiwari M, Sharma D, Trivedi PK, 2014. Artificial microRNA mediated gene silencing in plants: progress and perspectives. Plant Mol Biol, 86(1-2):1–18. https://doi.org/10.1007/s11103-014-0224-7
Tsang FHC, Au SLK, Wei L, et al., 2015. Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int, 35(5):1597–1606. https://doi.org/10.1111/liv.12746
Valiunas V, Wang HZ, Li L, et al., 2015. A comparison of two cellular delivery mechanisms for small interfering RNA. Physiol Rep, 3(2):e12286. https://doi.org/10.14814/phy2.12286
van der Krol AR, Mol JN, Stuitje AR, 1988. Modulation of eukaryotic gene expression by complementary RNA or DNA sequences. Biotechniques, 6(10):958–976.
van der Meer IM, Stam ME, van Tunen AJ, et al., 1992. Antisense inhibition of flavonoid biosynthesis in petunia anthers results in male sterility. Plant Cell, 4(3):253–262. https://doi.org/10.1105/tpc.4.3.253
Verstegen MMA, Pan QW, van der Laan LJW, 2015. Gene therapies for hepatitis C virus. In: Berkhout B, Ertl HCJ, Weinberg MS (Eds.), Gene Therapy for HIV and Chronic Infections. Springer, New York, NY, p.1–29. https://doi.org/10.1007/978-1-4939-2432-5_1
Villegas VE, Zaphiropoulos PG, 2015. Neighboring gene regulation by antisense long non-coding RNAs. Int J Mol Sci, 16(2):3251–3266. https://doi.org/10.3390/ijms16023251
Wakita T, Moradpour D, Tokushihge K, et al., 1999. Antiviral effects of antisense RNA on hepatitis C virus RNA translation and expression. J Med Virol, 57(3):217–222. https://doi.org/10.1002/(Sici)1096-9071(199903)57:3<217::Aid-Jmv1glt3.0.Co;2-X
Wang LW, Min JE, Zang X, et al., 2017. Characterizing human immunodeficiency virus antiretroviral therapy interruption and resulting disease progression using populationlevel data in British Columbia, 1996–2015. Clin Infect Dis, 65(9):1496–1503. https://doi.org/10.1093/cid/cix570
Wang TH, Zhong YH, Huang W, et al., 2005. Antisense inhibition of xylitol dehydrogenase gene, xdh1 from Trichoderma reesei. Lett Appl Microbiol, 40(6):424–429. https://doi.org/10.1111/j.1472-765X.2005.01685.x
Ward AM, Rekosh D, Hammarskjold ML, 2009. Trafficking through the Rev/RRE pathway is essential for efficient inhibition of human immunodeficiency virus type 1 by an antisense RNA derived from the envelope gene. J Virol, 83(2):940–952. https://doi.org/10.1128/Jvi.01520-08
Yang YP, Lin YH, Li LY, et al., 2015. Regulating malonyl-CoA metabolism via synthetic antisense RNAs for enhanced biosynthesis of natural products. Metab Eng, 29: 217–226. https://doi.org/10.1016/j.ymben.2015.03.018
Zhang LJ, Zhao ZJ, Feng ZJ, et al., 2012. RNA interferencemediated silencing of Stat5 induces apoptosis and growth suppression of hepatocellular carcinoma cells. Neoplasma, 59(3):302–309. https://doi.org/10.4149/neo_2012_039
Zhou K, He HX, Wu YY, et al., 2008. RNA interference of avian influenza virus H5N1 by inhibiting viral mRNA with siRNA expression plasmids. J Biotechnol, 135(2): 140–144. https://doi.org/10.1016/j.jbiotec.2008.03.007
Zhu XB, Zhi EL, Li Z, 2015. MOV10L1 in piRNA processing and gene silencing of retrotransposons during spermatogenesis. Reproduction, 149(5):R229–R235. https://doi.org/10.1530/REP-14-0569
Zuo LJ, Wang ZR, Tan YL, et al., 2016. piRNAs and their functions in the brain. Int J Hum Genet, 16(1-2):53–60. https://doi.org/10.1080/09723757.2016.11886278
Acknowledgements
We thank Mr. Gong CHENG (Department of Antibody Preparation, Wuxi Pharma Tech Co., Ltd., Wuxi, China) for helpful discussion.
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Project supported by the Natural Science Foundation of Jiangsu Province (No. BK20150149), the China Postdoctoral Science Foundation Grant (No. 2016M590410), and the Fundamental Research Funds for the Central Universities (No. JUSRP115A19), China
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Xu, Jz., Zhang, Jl. & Zhang, Wg. Antisense RNA: the new favorite in genetic research. J. Zhejiang Univ. Sci. B 19, 739–749 (2018). https://doi.org/10.1631/jzus.B1700594
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DOI: https://doi.org/10.1631/jzus.B1700594