Abstract
MicroRNAs are small (20–23 nucleotides) non-coding RNA molecules that mainly act as negative regulators of gene expression by binding to target mRNAs in their 3’UTR. In this chapter, we provide a brief account of the in silico and experimental tools available for researchers working in protein engineering in eukaryotic cell factories. In considering the wide influence of microRNAs, we place a special emphasis on the cellular effects associated with the manipulation of microRNA and high yield of protein production with reference to use in Chinese hamster ovary (CHO) expression systems.
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Arvey A, Larsson E, Sander C, Leslie CS, Marks DS (2011) Target mRNA abundance dilutes microRNA and siRNA activity. Mol Syst Biol 6:363
Barron N, Kumar N, Sanchez N, Doolan P, Clarke C, Meleady P, O’Sullivan F, Clynes M (2011) Engineering CHO cell growth and recombinant protein productivity by overexpression of miR-7. J Biotechnol 151:204–211
Bartel, DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233
Betel D, Wilson M, Gabow A, Marks DS, Sander C (2008) The microRNA.org resource: targets and expression. Nucleic Acids Res 36:D149–153
Borchert GM, Lanier W, Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13:1097–1101
Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113:25–36
Bueno MJ, Perez De Castro I, Malumbres M (2008) Control of cell proliferation pathways by microRNAs. Cell Cycle 7:3143–3148
Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. Rna 10:1957–1966
Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529
Clarke C, Doolan P, Barron N, Meleady P, O’Sullivan F, Gammell P, Melville M, Leonard M, Clynes M (2011) Large scale microarray profiling and coexpression network analysis of CHO cells identifies transcriptional modules associated with growth and productivity. J Biotechnol 155:350–359
Cui Q, Yu Z, Pan Y, Purisima EO, Wang E (2007) MicroRNAs preferentially target the genes with high transcriptional regulation complexity. Biochem Biophys Res Commun, 352:733–738
Ebert MS, Sharp PA (2010a) Emerging roles for natural microRNA sponges. Curr Biol 20:R858–861
Ebert MS, Sharp PA (2010b) MicroRNA sponges: progress and possibilities. Rna 16:2043–2050
Ebert M S, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726
Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105
Fussenegger M, Bailey JE (1998) Molecular regulation of cell-cycle progression and apoptosis in mammalian cells: implications for biotechnology. Biotechnol Prog 14:807–833
Gammell P, Barron N, Kumar N, Clynes M (2007) Initial identification of low temperature and culture stage induction of miRNA expression in suspension CHO-K1 cells. J Biotechnol 130:213–218
Godfried Sie CP, Kuchka M (2011) RNA editing adds flavor to complexity. Biochemistry (Mosc) 76:869–881
Gommans WM (2011) A-to-I editing of microRNAs: Regulating the regulators? Semin Cell Dev Biol.
Hackl M, Jakobi T, Blom J, Doppmeier D, Brinkrolf K, Szczepanowski R, Bernhart SH, Siederdissen CH, Bort JA, Wieser M, Kunert R, Jeffs S Hofacker I L, Goesmann A, Puhler A, Borth N, Grillari J (2011) Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering. J Biotechnol 153:62–75
Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027
Hinske LC, Galante PA, Kuo WP, Ohno-Machado L (2010) A potential role for intragenic miRNAs on their hosts’ interactome. BMC Genomics 11:533
Hsu CW, Juan HF, Huang HC (2008) Characterization of microRNA-regulated protein-protein interaction network. Proteomics 8:1975–1979
Huang Y, Gu X (2011) A study of the evolution of human microRNAs by their apparent repression effectiveness on target genes. PLoS One 6:e25034
Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl Tm, Zamore PD (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838
Hwang HW, Wentzel EA, Mendell JT (2009) Cell-cell contact globally activates microRNA biogenesis. Proc Natl Acad Sci USA 106:7016–7021
Ibanez-Ventoso C, Vora M, Driscoll M (2008) Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PLoS One 3:e2818
Johnson KC, Jacob NM, Nissom PM, Hackl M, Lee LH, Yap M, Hu WS (2010) Conserved MicroRNAs in Chinese hamster ovary cell lines. Biotechnol Bioeng.
Kantardjieff A, Nissom PM, Chuah SH, Yusufi F, Jacob NM, Mulukutla BC, Yap M, Hu WS (2009) Developing genomic platforms for Chinese hamster ovary cells. Biotechnol Adv 27:1028–1035
Kertesz M, Lovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39:1278–1284
Kim HJ, Kim YH, Lee DS, Chung JK, Kim S (2008) In vivo imaging of functional targeting of miR-221 in papillary thyroid carcinoma. J Nucl Med 49:1686–1693
Kim JY, Kim YG, Lee GM (2011) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93:917–930
Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139
Kim YK, Kim VN (2007) Processing of intronic microRNAs. Embo J 26:775–783
Kiryu H, TeraI G, Imamura O, Yoneyama H, Suzuki K, Asai K (2011) A detailed investigation of accessibilities around target sites of siRNAs and miRNAs. Bioinformatics 27:1788–1797
Koh TC, Lee YY, Chang SQ, Nissom PM (2009) Identification and expression analysis of miRNAs during batch culture of HEK-293 cells. J Biotechnol 140:149–155
Kong YW, Cannell IG, De Moor CH, Hill K, Garside PG, Hamilton TL, Meijer HA, Dobbyn HC, Stoneley M, Spriggs KA, Willis AE, Bushell M (2008) The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene. Proc Natl Acad Sci USA 105:8866–8871
Kozomara A, Griffiths-Jones S (2010) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152–157
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, Macmenamin P, Da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003) New microRNAs from mouse and human. Rna 9:175–179
Lau PW, Macrae IJ (2009) The molecular machines that mediate microRNA maturation. J Cell Mol Med 13:54–60
Lee J, Li Z, Brower-Sinning R, John B (2007) Regulatory circuit of human microRNA biogenesis. PLoS Comput Biol 3:e67
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20
Li L, Xu J, Yang D, Tan X, Wang H (2010) Computational approaches for microRNA studies: a review. Mamm Genome 21:1–12
Lin N, Davis A, Bahr S, Borgschulte T, Achtien K, Kayser K (2011) Profiling highly conserved microrna expression in recombinant IgG-producing and parental chinese hamster ovary cells. Biotechnol Prog.
Melville M, Doolan P, Mounts W, Barron N, Hann L, Leonard M, Clynes M, Charlebois T (2011) Development and characterization of a Chinese hamster ovary cell-specific oligonucleotide microarray. Biotechnol Lett 33:1773–1779
Min H, Yoon S (2010) Got target? Computational methods for microRNA target prediction and their extension. Exp Mol Med 42:233–244
Nam S, Kim B, Shin S, Lee S (2008) miRGator: an integrated system for functional annotation of microRNAs. Nucleic Acids Res 36:D159–164
Nissom PM, Sanny A, Kok YJ, Hiang YT, Chuah SH, Shing TK, Lee YY, Wong KT, Hu WS, Sim MY, Philp R (2006) Transcriptome and proteome profiling to understanding the biology of high productivity CHO cells. Mol Biotechnol 34:125–140
Park SY, Lee JH, Ha M, Nam JW, Kim VN (2009) miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol 16:23–29
Qiu C, Wang J, Yao P, Wang E, Cui Q (2010) microRNA evolution in a human transcription factor and microRNA regulatory network. BMC Syst Biol 4:90
Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86
Saj A, Lai EC (2011) Control of microRNA biogenesis and transcription by cell signaling pathways. Curr Opin Genet Dev 21:504–510
Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB (2008) Proliferating cells express mRNAs with shortened 3’ untranslated regions and fewer microRNA target sites. Science 320:1643–1647
Stern-Ginossar N, Gur C, Biton M, Horwitz E, Elboim M, Stanietsky N, Mandelboim M, Mandelboim O (2008) Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nat Immunol 9:1065–1073
Suzuki HI, Miyazono K (2010) Dynamics of microRNA biogenesis: crosstalk between p53 network and microRNA processing pathway. J Mol Med (Berl) 88:1085–1094
Tanguay RL, Gallie DR (1996) Translational efficiency is regulated by the length of the 3’ untranslated region. Mol Cell Biol 16:146–156
Trummer E, Fauland K, Seidinger S, Schriebl K, Lattenmayer C, Kunert R, Vorauer-Uhl K, Weik R, Borth N, Katinger H, Muller D (2006) Process parameter shifting: Part II. Biphasic cultivation-A tool for enhancing the volumetric productivity of batch processes using Epo-Fc expressing CHO cells. Biotechnol Bioeng 94:1045–1052
Westholm JO, Lai EC (2011) Mirtrons: microRNA biogenesis via splicing. Biochimie 93:1897–1904
Wijnhoven BP, Michael MZ, Watson DI (2007) MicroRNAs and cancer. Br J Surg 94:23–30
Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234
Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398
Xu X, Nagarajan H, Lewis NE, Pan S, Cai Z, Liu X, Chen W, Xie M, Wang W, Hammond S, Andersen MR, Neff N, Passarelli B, Koh W, Fan HC, Wang J, Gui Y, Lee KH, Betenbaugh MJ, Quake SR, Famili I, Palsson BO, Wang J (2011) The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nat Biotechnol 29:735–741
Yang F, Zhang L, Wang F, Wang Y, Huo XS, Yin YX, Wang YQ, Zhang L, Sun SH (2011) Modulation of the unfolded protein response is the core of microRNA-122-involved sensitivity to chemotherapy in hepatocellular carcinoma. Neoplasia 13:590–600
Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, Nishikura K (2006) Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol 13:13–21
Yee JC, De Leon Gatti M, Philp RJ, Yap M, Hu WS (2008) Genomic and proteomic exploration of CHO and hybridoma cells under sodium butyrate treatment. Biotechnol Bioeng 99:1186–1204
Yoon SK, Kim SH, Lee GM (2003a) Effect of low culture temperature on specific productivity and transcription level of anti-4–1BB antibody in recombinant Chinese hamster ovary cells. Biotechnol Prog 19:1383–1386
Yoon SK, Yand SJ, Lee GM (2003b) Effect of low culture temperature on specific productivity, transcription level, and heterogeneity of erythropoietin in Chinese hamster ovary cells. Biotechnol Bioeng 82:289–298
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Jossé, L., Zhang, L., Smales, C. (2012). A General Introduction to MicroRNAs, Their Investigation and Exploitation in CHO Cell Lines. In: Barron, N. (eds) MicroRNAs as Tools in Biopharmaceutical Production. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5128-6_1
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DOI: https://doi.org/10.1007/978-94-007-5128-6_1
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