Abstract
From analysis of deep-sequencing data it is apparent that sequence differences occur between the genome and miRNAs. Changes from genomic A to an apparent G in miRNA can be accounted for by the editing activity of ADARs. Questions that arise from this observation are: How many miRNAs are edited and to what frequency? Is there a specific step in the biogenesis of miRNAs that is preferentially susceptible to editing by ADARs? However the key question is whether editing affects the downstream activity of miRNAs. Despite much evidence that miRNAs are edited, critical examination of the functional data shows a dearth of examples where editing has been demonstrated to actually affect the downstream miRNA activity in vivo. Even where it is demonstrated that RNA editing can affect biogenesis or targeting of a particular miRNA, effects may be limited by redundancy within the miRNA network.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Heale BSE, M.A. O’Connell. Biological Roles of ADARs. In: Grosjean H, ed. DNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution. Austin: Landes Bioscience; 2009; 243–258.
Sommer B, Kohler M, Sprengel R et al. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 1991; 67(1):11–19.
Levanon EY, Eisenberg E, Yelin R et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 2004; 22(8): 1001–1005.
Adams MD, Celniker SE, Holt RA et al. The genome sequence of Drosophila melanogaster. Science 2000; 287(5461):2185–2195.
Venter JC, Adams MD, Myers EW et al. The sequence of the human genome. Science 2001; 291(sn5507):1304–1351.
Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 1995; 15(10):5376–5388.
Steitz TA. Similarities and differences between RNA and DNA recognition by proteins. In: Gesteland RF, Atkins JF, eds. “The RNA World”. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 1993:219–237.
Bevilacqua PC, Cech TR. Minor-groove recognition of double-stranded RNA by the double-stranded RNA-binding domain from the RNA-activated protein kinase PKR. Biochemistry 1996; 35(31):9983–9994.
Reid JG, Nagaraja AK, Lynn FC et al. Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5′-seed/cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes. Genome Res 2008; 18(10):1571–1581.
Lu S, Sun YH, Chiang VL. Adenylation of plant miRNAs. Nucleic Acids Res 2009; 37(6):1878–1885.
Li J, Yang Z, Yu B et al. Methylation protects miRNAs and siRNAs from a 3′-end uridylation activity in Arabidopsis. Curr Biol 2005; 15(16):1501–1507.
Ramachandran V, Chen X. Degradation of microRNAs by a family of exoribonucleases in Arabidopsis. Science 2008; 321(5895):1490–1492.
Heo I, Joo C, Cho J et al. Lin28 mediates the terminal uridylation of let-7 precursor microRNA. Mol Cell 2008; 32(2):276–284.
Katoh T, Sakaguchi Y, Miyauchi K et al. Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 2009; 23(4):433–438.
Blow MJ, Grocock RJ, van Dongen S et al. RNA editing of human microRNAs. Genome Biol 2006; 7(4):R27.
Landgraf P, Rusu M, Sheridan R et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 2007; 129(7):1401–1414.
Kawahara Y, Megraw M, Kreider E et al. Frequency and fate of microRNA editing in human brain. Nucleic Acids Res 2008; 36(16):5270–5280.
Jin W, Grant JR, Stothard P et al. Characterization of bovine miRNAs by sequencing and bioinformatics analysis. BMC Mol Biol 2009; 10:90.
Wu H, Neilson JR, Kumar P et al. miRNA profiling of naive, effector and memory CD8 T-cells. PLoS One 2007; 2(10):e1020.
Luciano DJ, Mirsky H, Vendetti NJ et al. RNA editing of a miRNA precursor. RNA 2004; 10(8): 1174–1177.
Yang W, Chendrimada TP, Wang Q et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol 2006; 13(1):13–21.
Heale BS, Keegan LP, McGurk L et al. Editing independent effects of ADARs on the miRNA/siRNA pathways. EMBO J 2009; 28(20):3145–3156.
Kawahara Y, Zinshteyn B, Chendrimada TP et al. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Reports 2007; 8(8):763–769.
Caudy AA, Ketting RF, Hammond SM et al. A micrococcal nuclease homologue in RNAi effector complexes. Nature 2003; 425(6956):411–414.
Scadden AD. The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat Struct Mol Biol 2005; 12(6):489–496.
Pfeffer S, Sewer A, Lagos-Quintana M et al. Identification of microRNAs of the herpesvirus family. Nat Methods 2005; 2(4):269–276.
Kawahara Y, Zinshteyn B, Sethupathy P et al. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 2007; 315(5815): 1137–1140.
Guil S, Caceres JF. The multifunctional RNA-binding protein hnRNP Al is required for processing of miR-18a. Nat Struct Mol Biol 2007; 14(7):591–596.
Borchert GM, Gilmore BL, Spengler RM et al. Adenosine deamination in human transcripts generates novel microRNA binding sites. Hum Mol Genet 2009; 18(24):4801–4807.
Morse DP, Aruscavage PJ, Bass BL. RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA. Proc Natl Acad Sci USA 2002; 99(12):7906–7911.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Landes Bioscience and Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Heale, B.S.E., Keegan, L.P., O’Connell, M.A. (2010). The Effect of RNA Editing and ADARs on miRNA Biogenesis and Function. In: Großhans, H. (eds) Regulation of microRNAs. Advances in Experimental Medicine and Biology, vol 700. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7823-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-4419-7823-3_8
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-7822-6
Online ISBN: 978-1-4419-7823-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)