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RNA Activation pp 81–89Cite as

miRNA-Mediated RNA Activation in Mammalian Cells

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 983))

Abstract

MicroRNA (miRNA or miR) is a small noncoding RNA molecule ~22 nucleotides in size, which is found in plants, animals, and some viruses. miRNAs are thought to primarily down regulate gene expression by binding to 3′ untranslated regions of target transcripts, thereby triggering mRNA cleavage or repression of translation. Recently, evidence has emerged that miRNAs can interact with the promoter and activate gene expression. This mechanism, called RNA activation (RNAa), is a process of transcriptional activation where the direct interaction of miRNA on the promoter triggers the recruitment of transcription factors and RNA-Polymerase-II on the promoter to activate gene transcription. To date, very little is known about the mechanism by which miRNA regulates RNA activation (RNAa) and their role in tumor progression. This is an emerging field in RNA biology. In this chapter, we describe the mechanisms utilized by miRNAs to activate transcription.

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References

  1. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107(7):823–826

    Article  CAS  PubMed  Google Scholar 

  2. Ambros V, Lee RC, Lavanway A, Williams PT, Jewell D (2003) MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol 13(10):807–818

    Article  CAS  PubMed  Google Scholar 

  3. Azlan A, Dzaki N, Azzam G (2016) Argonaute: the executor of small RNA function. J Genet Genomics 43(8):481–494. doi:10.1016/j.jgg.2016.06.002

    Article  PubMed  Google Scholar 

  4. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129(4):823–837. doi:10.1016/j.cell.2007.05.009

    Article  CAS  PubMed  Google Scholar 

  5. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  CAS  PubMed  Google Scholar 

  6. Britten RJ, Davidson EH (1969) Gene regulation for higher cells: a theory. Science 165(3891):349–357

    Article  CAS  PubMed  Google Scholar 

  7. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y (2002) Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science 298(5595):1039–1043. doi:10.1126/science.1076997

    Article  CAS  PubMed  Google Scholar 

  8. Chaluvally-Raghavan P, Jeong KJ, Pradeep S, Silva AM, Yu S, Liu W, Moss T, Rodriguez-Aguayo C, Zhang D, Ram P, Liu J, Lu Y, Lopez-Berestein G, Calin GA, Sood AK, Mills GB (2016) Direct upregulation of STAT3 by MicroRNA-551b-3p deregulates growth and metastasis of ovarian cancer. Cell Rep 15(7):1493–1504. doi:10.1016/j.celrep.2016.04.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dykxhoorn DM, Novina CD, Sharp PA (2003) Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4(6):457–467. doi:10.1038/nrm1129

    Article  CAS  PubMed  Google Scholar 

  10. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811. doi:10.1038/35888

    Article  CAS  PubMed  Google Scholar 

  11. Huang V, Qin Y, Wang J, Wang XL, Place RF, Lin GT, Lue TF, Li LC (2010) RNAa is conserved in mammalian cells. Plos One 5(1). doi:ARTN e8848 10.1371/journal.pone.0008848

  12. Huang V, Place RF, Portnoy V, Wang J, Qi Z, Jia Z, Yu A, Shuman M, Yu J, Li LC (2012) Upregulation of cyclin B1 by miRNA and its implications in cancer. Nucleic Acids Res 40(4):1695–1707. doi:10.1093/nar/gkr934

    Article  CAS  PubMed  Google Scholar 

  13. Huang V, Zheng J, Qi Z, Wang J, Place RF, Yu J, Li H, Li LC (2013) Ago1 interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells. PLoS Genet 9(9):e1003821. doi:10.1371/journal.pgen.1003821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hutvagner G, Simard MJ (2008) Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 9(1):22–32. doi:10.1038/nrm2321

    Article  CAS  PubMed  Google Scholar 

  15. Jain R, Iglesias N, Moazed D (2016) Distinct functions of argonaute slicer in siRNA maturation and heterochromatin formation. Mol Cell 63(2):191–205. doi:10.1016/j.molcel.2016.05.039

    Article  CAS  PubMed  Google Scholar 

  16. Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR (2007) Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol 3(3):166–173. doi:10.1038/nchembio860

    Article  CAS  PubMed  Google Scholar 

  17. Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, Enokida H, Dahiya R (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103(46):17337–17342. doi:10.1073/pnas.0607015103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lopez P, Wagner KD, Hofman P, Van Obberghen E (2016) RNA activation of the vascular endothelial growth factor gene (VEGF) promoter by double-stranded RNA and hypoxia: role of noncoding VEGF promoter transcripts. Mol Cell Biol 36(10):1480–1493. doi:10.1128/MCB.01096-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Matsui M, Chu Y, Zhang H, Gagnon KT, Shaikh S, Kuchimanchi S, Manoharan M, Corey DR, Janowski BA (2013) Promoter RNA links transcriptional regulation of inflammatory pathway genes. Nucleic Acids Res 41(22):10086–10109. doi:10.1093/nar/gkt777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Matsui M, Li L, Janowski BA, Corey DR (2015) Reduced expression of argonaute 1, argonaute 2, and TRBP changes levels and intracellular distribution of RNAi factors. Sci Rep 5:12855. doi:10.1038/srep12855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Matsui M, Prakash TP, Corey DR (2016) Argonaute 2-dependent regulation of gene expression by single-stranded miRNA mimics. Mol Ther 24(5):946–955. doi:10.1038/mt.2016.39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15(2):185–197. doi:10.1016/j.molcel.2004.07.007

    Article  CAS  PubMed  Google Scholar 

  23. Pasini D, Bracken AP, Hansen JB, Capillo M, Helin K (2007) The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol 27(10):3769–3779. doi:10.1128/MCB.01432-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408(6808):86–89. doi:10.1038/35040556

    Article  CAS  PubMed  Google Scholar 

  25. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105(5):1608–1613. doi:10.1073/pnas.0707594105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Place RF, Noonan EJ, Foldes-Papp Z, Li LC (2010) Defining features and exploring chemical modifications to manipulate RNAa activity. Curr Pharm Biotechnol 11(5):518–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Portnoy V, Huang V, Place RF, Li LC (2011) Small RNA and transcriptional upregulation. Wiley Interdiscip Rev RNA 2(5):748–760. doi:10.1002/wrna.90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reebye V, Saetrom P, Mintz PJ, Huang KW, Swiderski P, Peng L, Liu C, Liu X, Lindkaer-Jensen S, Zacharoulis D, Kostomitsopoulos N, Kasahara N, Nicholls JP, Jiao LR, Pai M, Spalding DR, Mizandari M, Chikovani T, Emara MM, Haoudi A, Tomalia DA, Rossi JJ, Habib NA (2014) Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo. Hepatology 59(1):216–227. doi:10.1002/hep.26669

    Article  CAS  PubMed  Google Scholar 

  29. Saini HK, Griffiths-Jones S, Enright AJ (2007) Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci U S A 104(45):17719–17724. doi:10.1073/pnas.0703890104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schurmann N, Trabuco LG, Bender C, Russell RB, Grimm D (2013) Molecular dissection of human argonaute proteins by DNA shuffling. Nat Struct Mol Biol 20(7):818–826. doi:10.1038/nsmb.2607

    Article  PubMed  Google Scholar 

  31. Turunen MP, Lehtola T, Heinonen SE, Assefa GS, Korpisalo P, Girnary R, Glass CK, Vaisanen S, Yla-Herttuala S (2009) Efficient regulation of VEGF expression by promoter-targeted lentiviral shRNAs based on epigenetic mechanism: a novel example of epigenetherapy. Circ Res 105(6):604–609. doi:10.1161/CIRCRESAHA.109.200774

    Article  CAS  PubMed  Google Scholar 

  32. Vaucheret H, Vazquez F, Crete P, Bartel DP (2004) The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev 18(10):1187–1197. doi:10.1101/gad.1201404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang X, Wang J, Huang V, Place RF, Li LC (2012) Induction of NANOG expression by targeting promoter sequence with small activating RNA antagonizes retinoic acid-induced differentiation. Biochem J 443(3):821–828. doi:10.1042/BJ20111491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang T, Li M, Yuan H, Zhan Y, Xu H, Wang S, Yang W, Liu J, Ye Z, Li LC (2013) saRNA guided iNOS up-regulation improves erectile function of diabetic rats. J Urol 190(2):790–798. doi:10.1016/j.juro.2013.03.043

    Article  CAS  PubMed  Google Scholar 

  35. Wei Y, Li L, Wang D, Zhang CY, Zen K (2014) Importin 8 regulates the transport of mature microRNAs into the cell nucleus. J Biol Chem 289(15):10270–10275. doi:10.1074/jbc.C113.541417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yue X, Schwartz JC, Chu Y, Younger ST, Gagnon KT, Elbashir S, Janowski BA, Corey DR (2010) Transcriptional regulation by small RNAs at sequences downstream from 3′ gene termini. Nat Chem Biol 6(8):621–629. doi:10.1038/nchembio.400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

P. Chaluvally-Raghavan is supported by the Liz-Tilberis Career Development Award and the Ann Schreiber Scholar Award from the Ovarian Cancer Research Foundation and funds from the Marsha Rivkin Center for Ovarian Cancer Research. Ramani Ramchandran is supported by endowment funds from the Department of OBGYN at MCW, programmatic support funds from the Department of Pediatrics, Children’s Research Institute, and NIH grants HL123338, HL112639, HL033833, and HL128374.

Conflict of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Ramani Ramchandran & Pradeep Chaluvally-Raghavan

  2. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Ramani Ramchandran

  3. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Pradeep Chaluvally-Raghavan

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  1. Ramani Ramchandran
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  2. Pradeep Chaluvally-Raghavan
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Correspondence to Pradeep Chaluvally-Raghavan .

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Editors and Affiliations

  1. Laboratory of Molecular Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

    Long-Cheng Li

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Ramchandran, R., Chaluvally-Raghavan, P. (2017). miRNA-Mediated RNA Activation in Mammalian Cells. In: Li, LC. (eds) RNA Activation. Advances in Experimental Medicine and Biology, vol 983. Springer, Singapore. https://doi.org/10.1007/978-981-10-4310-9_6

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