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PMID: 20924405 Published · ppublish English Journal Article Review

Desperately seeking microRNA targets.

Nature structural & molecular biology ·Vol. 17 ·No. 10 ·2010-10-00 ·Pages 1169-74

Thomas M, Lieberman J, Lal A

Abstract

MicroRNAs (miRNAs) suppress gene expression by inhibiting translation, promoting mRNA decay or both. Each miRNA may regulate hundreds of genes to control the cell's response to developmental and other environmental cues. The best way to understand the function of a miRNA is to identify the genes that it regulates. Target gene identification is challenging because miRNAs bind to their target mRNAs by partial complementarity over a short sequence, suppression of an individual target gene is often small, and the rules of targeting are not completely understood. Here we review computational and experimental approaches to the identification of miRNA-regulated genes. The examination of changes in gene expression that occur when miRNA expression is altered and biochemical isolation of miRNA-associated transcripts complement target prediction algorithms. Bioinformatic analysis of over-represented pathways and nodes in protein-DNA interactomes formed from experimental candidate miRNA gene target lists can focus attention on biologically significant target genes.

MeSH Terms
3' Untranslated Regions Algorithms Animals Autoantigens/physiology Base Pairing Base Sequence Binding Sites Caenorhabditis elegans/genetics Computational Biology/methods Databases, Genetic Gene Expression Regulation Gene Knockdown Techniques Gene Regulatory Networks Humans Mice MicroRNAs/physiology Oligonucleotide Array Sequence Analysis Proteomics RNA Stability RNA, Messenger/genetics,metabolism RNA-Binding Proteins/physiology RNA-Induced Silencing Complex/physiology
Chemicals
3' Untranslated Regions Autoantigens MicroRNAs RNA, Messenger RNA-Binding Proteins RNA-Induced Silencing Complex TNRC6A protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Thomas Marshall
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Lieberman Judy
Lal Ashish
References (74)
74 references, click to expand
  1. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation.
    Science. 2007 Mar 16;315(5818):1576-9 PMID: 17322030
  2. Alternative isoform regulation in human tissue transcriptomes.
    Nature. 2008 Nov 27;456(7221):470-6 PMID: 18978772
  3. p16(INK4a) translation suppressed by miR-24.
    PLoS One. 2008 Mar 26;3(3):e1864 PMID: 18365017
  4. Identification of human microRNA targets from isolated argonaute protein complexes.
    RNA Biol. 2007 Jun;4(2):76-84 PMID: 17637574
  5. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes.
    Cell. 2006 Sep 22;126(6):1203-17 PMID: 16990141
  6. Combinatorial microRNA target predictions.
    Nat Genet. 2005 May;37(5):495-500 PMID: 15806104
  7. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation.
    Mol Cell. 2008 May 23;30(4):460-71 PMID: 18498749
  8. Lost in translation: an assessment and perspective for computational microRNA target identification.
    Bioinformatics. 2009 Dec 1;25(23):3049-55 PMID: 19789267
  9. mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts.
    Nat Methods. 2008 Sep;5(9):813-9 PMID: 19160516
  10. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
    Nature. 2005 Feb 17;433(7027):769-73 PMID: 15685193
  11. Predicting microRNA targets and functions: traps for the unwary.
    Nat Methods. 2009 Jun;6(6):397-8 PMID: 19478799
  12. A biochemical approach to identifying microRNA targets.
    Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19291-6 PMID: 18042700
  13. Biogenesis of small RNAs in animals.
    Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39 PMID: 19165215
  14. Most mammalian mRNAs are conserved targets of microRNAs.
    Genome Res. 2009 Jan;19(1):92-105 PMID: 18955434
  15. Human MicroRNA targets.
    PLoS Biol. 2004 Nov;2(11):e363 PMID: 15502875
  16. Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets.
    Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):15085-90 PMID: 19706460
  17. MicroRNA targeting specificity in mammals: determinants beyond seed pairing.
    Mol Cell. 2007 Jul 6;27(1):91-105 PMID: 17612493
  18. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps.
    Nature. 2009 Jul 23;460(7254):479-86 PMID: 19536157
  19. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury.
    Genes Dev. 2009 Sep 15;23(18):2166-78 PMID: 19720868
  20. Progressive lengthening of 3' untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7028-33 PMID: 19372383
  21. Silencing of microRNAs in vivo with 'antagomirs'.
    Nature. 2005 Dec 1;438(7068):685-9 PMID: 16258535
  22. GW182 family proteins are crucial for microRNA-mediated gene silencing.
    Trends Cell Biol. 2007 Aug;17(8):411-6 PMID: 17766119
  23. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation.
    Nature. 2008 Oct 23;455(7216):1124-8 PMID: 18806776
  24. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression.
    Mol Cell Biol. 2007 Mar;27(6):2240-52 PMID: 17242205
  25. The microRNA.org resource: targets and expression.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53 PMID: 18158296
  26. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs.
    Nat Biotechnol. 2009 Jun;27(6):549-55 PMID: 19465925
  27. RAS is regulated by the let-7 microRNA family.
    Cell. 2005 Mar 11;120(5):635-47 PMID: 15766527
  28. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements.
    Mol Cell. 2009 Sep 11;35(5):610-25 PMID: 19748357
  29. Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs.
    RNA. 2008 Dec;14(12):2580-96 PMID: 18978028
  30. microRNA target predictions in animals.
    Nat Genet. 2006 Jun;38 Suppl:S8-13 PMID: 16736023
  31. Essential and overlapping functions for mammalian Argonautes in microRNA silencing.
    Genes Dev. 2009 Feb 1;23(3):304-17 PMID: 19174539
  32. Isolation of microRNA targets using biotinylated synthetic microRNAs.
    Methods. 2007 Oct;43(2):162-5 PMID: 17889804
  33. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis.
    Mol Cell. 2007 Jun 8;26(5):745-52 PMID: 17540599
  34. The role of site accessibility in microRNA target recognition.
    Nat Genet. 2007 Oct;39(10):1278-84 PMID: 17893677
  35. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease.
    Cell Death Differ. 2009 Dec;16(12):1590-8 PMID: 19816508
  36. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  37. Small silencing RNAs: an expanding universe.
    Nat Rev Genet. 2009 Feb;10(2):94-108 PMID: 19148191
  38. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
    Cell. 1993 Dec 3;75(5):855-62 PMID: 8252622
  39. Expanding the microRNA targeting code: functional sites with centered pairing.
    Mol Cell. 2010 Jun 25;38(6):789-802 PMID: 20620952
  40. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions.
    Nat Struct Mol Biol. 2006 Sep;13(9):849-51 PMID: 16921378
  41. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression.
    Cell. 2007 Dec 14;131(6):1097-108 PMID: 18083100
  42. Stable Argonaute2 overexpression differentially regulates microRNA production.
    Biochim Biophys Acta. 2009 Feb;1789(2):153-9 PMID: 19064005
  43. Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance.
    PLoS One. 2008 May 07;3(5):e2126 PMID: 18461144
  44. Computational methods to identify miRNA targets.
    Semin Cell Dev Biol. 2010 Sep;21(7):738-44 PMID: 20079866
  45. Human mitochondrial tRNAMet is exported to the cytoplasm and associates with the Argonaute 2 protein.
    RNA. 2005 Jun;11(6):849-52 PMID: 15872185
  46. The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes.
    J Biol Chem. 2007 Mar 16;282(11):8256-64 PMID: 17220301
  47. The let-7 microRNA represses cell proliferation pathways in human cells.
    Cancer Res. 2007 Aug 15;67(16):7713-22 PMID: 17699775
  48. Isolation of microRNA targets by miRNP immunopurification.
    RNA. 2007 Aug;13(8):1198-204 PMID: 17592038
  49. Widespread changes in protein synthesis induced by microRNAs.
    Nature. 2008 Sep 4;455(7209):58-63 PMID: 18668040
  50. Dynamic regulation of miRNA expression in ordered stages of cellular development.
    Genes Dev. 2007 Mar 1;21(5):578-89 PMID: 17344418
  51. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
    Cell. 2010 Apr 2;141(1):129-41 PMID: 20371350
  52. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  53. miR-19 is a key oncogenic component of mir-17-92.
    Genes Dev. 2009 Dec 15;23(24):2839-49 PMID: 20008935
  54. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.
    Cell. 2005 Jan 14;120(1):15-20 PMID: 15652477
  55. Revisiting the principles of microRNA target recognition and mode of action.
    Nat Rev Mol Cell Biol. 2009 Feb;10(2):141-8 PMID: 19145236
  56. The functions of animal microRNAs.
    Nature. 2004 Sep 16;431(7006):350-5 PMID: 15372042
  57. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  58. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.
    Cell. 2009 Aug 21;138(4):673-84 PMID: 19703394
  59. Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA.
    PLoS Biol. 2009 Nov;7(11):e1000238 PMID: 19901979
  60. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53.
    Blood. 2009 Sep 3;114(10):2181-92 PMID: 19584398
  61. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas.
    Genes Dev. 2009 Dec 15;23(24):2806-11 PMID: 20008931
  62. miR-148 targets human DNMT3b protein coding region.
    RNA. 2008 May;14(5):872-7 PMID: 18367714
  63. Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs.
    Nat Struct Mol Biol. 2009 Feb;16(2):144-50 PMID: 19182800
  64. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia.
    Nat Cell Biol. 2010 Apr;12(4):372-9 PMID: 20190740
  65. A guide through present computational approaches for the identification of mammalian microRNA targets.
    Nat Methods. 2006 Nov;3(11):881-6 PMID: 17060911
  66. Regulation of MicroRNA Biogenesis: A miRiad of mechanisms.
    Cell Commun Signal. 2009 Aug 10;7:18 PMID: 19664273
  67. The impact of microRNAs on protein output.
    Nature. 2008 Sep 4;455(7209):64-71 PMID: 18668037
  68. Many roads to maturity: microRNA biogenesis pathways and their regulation.
    Nat Cell Biol. 2009 Mar;11(3):228-34 PMID: 19255566
  69. The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR.
    Genes Dev. 2004 Jan 15;18(2):132-7 PMID: 14729570
  70. Comprehensive discovery of endogenous Argonaute binding sites in Caenorhabditis elegans.
    Nat Struct Mol Biol. 2010 Feb;17(2):173-9 PMID: 20062054
  71. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells.
    Nat Struct Mol Biol. 2009 May;16(5):492-8 PMID: 19377482
  72. MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1.
    Stem Cells. 2008 Jan;26(1):17-29 PMID: 17916804
  73. Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2.
    Mol Cell. 2007 Nov 30;28(4):598-613 PMID: 18042455
  74. Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites.
    Science. 2008 Jun 20;320(5883):1643-7 PMID: 18566288
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1921
Published
2010-10-00
Pages
1169-74
Language
English
Region
United States
NLM ID
101186374
Subset
IM
External Links
PubMed source DOI: 10.1038/nsmb.1921 View journal details
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