Skip to main content
SpringerLink
Log in
Book cover

Adenosine Deaminases Acting on RNA (ADARs) and A-to-I Editing pp 91–109Cite as

Modulation of MicroRNA Expression and Function by ADARs

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 353))

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by preventing the translation of specific messenger RNAs. Adenosine deaminases acting on RNAs (ADARs) catalyze adenosine-to-inosine (A-to-I) RNA editing, the conversion of adenosines into inosines, in double-stranded RNAs. Because inosine preferentially base pairs with cytidine, this conversion is equivalent to an adenosine to guanosine change. Over the past seven years, an increasing number of edited adenosines have been identified in miRNAs. Editing of miRNAs affects their biogenesis, causes their degradation or alters the set of messenger RNAs that they regulate. Recently, ADARs have been shown to also affect the miRNA phenomenon by sequestering miRNAs or by editing the messenger RNAs they regulate. This article reviews the recent attempts to identify miRNA editing sites and elucidate the effects of ADARs on miRNA expression and function.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

A:

Adenosine

I:

Inosine

G:

Guanosine

U:

Uridine

C:

Cytidine

UTR:

Untranslated region

dsRNA:

Double-stranded RNA

ADAR:

Adenosine deaminase acting on RNA

miRNA:

MicroRNA

pri-miRNA:

Primary miRNA

pre-miRNA:

Precursor miRNA

mRNA:

Messenger RNA

pre-mRNA:

Precursor messenger RNA

siRNA:

Small interfering RNA

cDNA:

Complementary DNA

Tudor-SN:

Tudor staphylococcal nuclease

EBV:

Epstein-Barr virus

DFFA:

DNA fragmentation factor alpha

PRPS1:

Phosphoribosyl pyrophosphate synthetase 1

References

  • Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22:2773–2785

    Article  PubMed  CAS  Google Scholar 

  • Bass BL (2002) RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 71:817–846

    Article  PubMed  CAS  Google Scholar 

  • Bass BL, Weintraub H (1988) An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55:1089–1098

    Article  PubMed  CAS  Google Scholar 

  • Berezikov E, Robine N, Samsonova A, Westholm JO, Naqvi A, Hung JH, Okamura K, Dai Q, Bortolamiol-Becet D, Martin R, Zhao Y, Zamore PD, Hannon GJ, Marra MA, Weng Z, Perrimon N, Lai EC (2011) Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res 21:203–215

    Article  PubMed  CAS  Google Scholar 

  • Blow MJ, Grocock RJ, van Dongen S, Enright AJ, Dicks E, Futreal PA, Wooster R, Stratton MR (2006) RNA editing of human microRNAs. Genome Biol 7:R27

    Article  PubMed  Google Scholar 

  • Borchert GM, Gilmore BL, Spengler RM, Xing Y, Lanier W, Bhattacharya D, Davidson BL (2009) Adenosine deamination in human transcripts generates novel microRNA binding sites. Hum Mol Genet 18:4801–4807

    Article  PubMed  CAS  Google Scholar 

  • Chiang HR, Schoenfeld LW, Ruby JG, Auyeung VC, Spies N, Baek D, Johnston WK, Russ C, Luo S, Babiarz JE, Blelloch R, Schroth GP, Nusbaum C, Bartel DP (2010) Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev 24:992–1009

    Article  PubMed  CAS  Google Scholar 

  • de Hoon MJ, Taft RJ, Hashimoto T, Kanamori-Katayama M, Kawaji H, Kawano M, Kishima M, Lassmann T, Faulkner GJ, Mattick JS, Daub CO, Carninci P, Kawai J, Suzuki H, Hayashizaki Y (2010) Cross-mapping and the identification of editing sites in mature microRNAs in high-throughput sequencing libraries. Genome Res 20:257–264

    Article  PubMed  Google Scholar 

  • Gottwein E, Cai X, Cullen BR (2006) A novel assay for viral microRNA function identifies a single nucleotide polymorphism that affects Drosha processing. J Virol 80:5321–5326

    Article  PubMed  CAS  Google Scholar 

  • Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27:91–105

    Article  PubMed  CAS  Google Scholar 

  • Heale BS, Keegan LP, McGurk L, Michlewski G, Brindle J, Stanton CM, Caceres JF, O’Connell MA (2009) Editing independent effects of ADARs on the miRNA/siRNA pathways. EMBO J 28:3145–3156

    Article  PubMed  CAS  Google Scholar 

  • Iizasa H, Wulff BE, Alla NR, Maragkakis M, Megraw M, Hatzigeorgiou A, Iwakiri D, Takada K, Wiedmer A, Showe L, Lieberman P, Nishikura K (2010) Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency. J Biol Chem 285:33358–33370

    Article  PubMed  CAS  Google Scholar 

  • Jin Y, Zhang W, Li Q (2009) Origins and evolution of ADAR-mediated RNA editing. IUBMB Life 61:572–578

    Article  PubMed  CAS  Google Scholar 

  • Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K (2007a) RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep 8:763–769

    Article  PubMed  CAS  Google Scholar 

  • Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K (2007b) Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315:1137–1140

    Article  PubMed  CAS  Google Scholar 

  • Kawahara Y, Megraw M, Kreider E, Iizasa H, Valente L, Hatzigeorgiou AG, Nishikura K (2008) Frequency and fate of microRNA editing in human brain. Nucleic Acids Res 36:5270–5280

    Article  PubMed  CAS  Google Scholar 

  • Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139

    Article  PubMed  CAS  Google Scholar 

  • Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610

    PubMed  CAS  Google Scholar 

  • Kuchenbauer F, Morin RD, Argiropoulos B, Petriv OI, Griffith M, Heuser M, Yung E, Piper J, Delaney A, Prabhu AL, Zhao Y, McDonald H, Zeng T, Hirst M, Hansen CL, Marra MA, Humphries RK (2008) In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res 18:1787–1797

    Article  PubMed  CAS  Google Scholar 

  • Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414

    Article  PubMed  CAS  Google Scholar 

  • Liang H, Landweber LF (2007) Hypothesis: RNA editing of microRNA target sites in humans? RNA 13:463–467

    Article  PubMed  CAS  Google Scholar 

  • Linsen SE, de Wit E, de Bruijn E, Cuppen E (2010) Small RNA expression and strain specificity in the rat. BMC Genomics 11:249

    Article  PubMed  Google Scholar 

  • Luciano DJ, Mirsky H, Vendetti NJ, Maas S (2004) RNA editing of a miRNA precursor. RNA 10:1174–1177

    Article  PubMed  CAS  Google Scholar 

  • Morin RD, O’Connor MD, Griffith M, Kuchenbauer F, Delaney A, Prabhu AL, Zhao Y, McDonald H, Zeng T, Hirst M, Eaves CJ, Marra MA (2008) Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res 18:610–621

    Article  PubMed  CAS  Google Scholar 

  • Nishikura K (2010) Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 79:321–349

    Article  PubMed  CAS  Google Scholar 

  • Okada C, Yamashita E, Lee SJ, Shibata S, Katahira J, Nakagawa A, Yoneda Y, Tsukihara T (2009) A high-resolution structure of the pre-microRNA nuclear export machinery. Science 326:1275–1279

    Article  PubMed  CAS  Google Scholar 

  • Ruby JG, Jan C, Player C, Axtell MJ, Lee W, Nusbaum C, Ge H, Bartel DP (2006) Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127:1193–1207

    Article  PubMed  CAS  Google Scholar 

  • Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10:389–402

    Article  PubMed  CAS  Google Scholar 

  • Scadden AD (2005) The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat Struct Mol Biol 12:489–496

    Article  PubMed  CAS  Google Scholar 

  • Scadden AD, Smith CW (2001) Specific cleavage of hyper-edited dsRNAs. EMBO J 20:4243–4252

    Article  PubMed  CAS  Google Scholar 

  • Schulte JH, Marschall T, Martin M, Rosenstiel P, Mestdagh P, Schlierf S, Thor T, Vandesompele J, Eggert A, Schreiber S, Rahmann S, Schramm A (2010) Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res 38:5919–5928

    Article  PubMed  CAS  Google Scholar 

  • Siomi H, Siomi MC (2010) Posttranscriptional regulation of microRNA biogenesis in animals. Mol Cell 38:323–332

    Article  PubMed  CAS  Google Scholar 

  • Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ (2009) SNPs in human miRNA genes affect biogenesis and function. RNA 15:1640–1651

    Article  PubMed  CAS  Google Scholar 

  • Suzuki H, Forrest AR, van Nimwegen E, Daub CO, Balwierz PJ, Irvine KM, Lassmann T, Ravasi T, Hasegawa Y, de Hoon MJ, Katayama S, Schroder K, Carninci P, Tomaru Y, Kanamori-Katayama M, Kubosaki A, Akalin A, Ando Y, Arner E, Asada M, Asahara H, Bailey T, Bajic VB, Bauer D, Beckhouse AG, Bertin N, Bjorkegren J, Brombacher F, Bulger E, Chalk AM, Chiba J, Cloonan N, Dawe A, Dostie J, Engstrom PG, Essack M, Faulkner GJ, Fink JL, Fredman D, Fujimori K, Furuno M, Gojobori T, Gough J, Grimmond SM, Gustafsson M, Hashimoto M, Hashimoto T, Hatakeyama M, Heinzel S, Hide W, Hofmann O, Hornquist M, Huminiecki L, Ikeo K, Imamoto N, Inoue S, Inoue Y, Ishihara R, Iwayanagi T, Jacobsen A, Kaur M, Kawaji H, Kerr MC, Kimura R, Kimura S, Kimura Y, Kitano H, Koga H, Kojima T, Kondo S, Konno T, Krogh A, Kruger A, Kumar A, Lenhard B, Lennartsson A, Lindow M, Lizio M, Macpherson C, Maeda N, Maher CA, Maqungo M, Mar J, Matigian NA, Matsuda H, Mattick JS, Meier S, Miyamoto S, Miyamoto-Sato E, Nakabayashi K, Nakachi Y, Nakano M, Nygaard S, Okayama T, Okazaki Y, Okuda-Yabukami H, Orlando V, Otomo J, Pachkov M, Petrovsky N et al (2009) The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet 41:553–562

    Article  PubMed  CAS  Google Scholar 

  • Wulff BE, Sakurai M, Nishikura K (2011) Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing. Nat Rev Genet 12:81–85

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Wang Q, Howell KL, Lee JT, Cho DS, Murray JM, Nishikura K (2005) ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells. J Biol Chem 280:3946–3953

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA

    Bjorn-Erik Wulff & Kazuko Nishikura

Authors
  1. Bjorn-Erik Wulff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuko Nishikura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bjorn-Erik Wulff .

Editor information

Editors and Affiliations

  1. , Dept. of Molecular, Cellular and Develop, University of California, Santa Barbara, Santa Barbara, 93106, California, USA

    Charles E. Samuel

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wulff, BE., Nishikura, K. (2011). Modulation of MicroRNA Expression and Function by ADARs. In: Samuel, C. (eds) Adenosine Deaminases Acting on RNA (ADARs) and A-to-I Editing. Current Topics in Microbiology and Immunology, vol 353. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_151

Download citation

Publish with us

Policies and ethics

Search

Navigation