Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
BioDrugs
Erschienen in: BioDrugs 2/2007

01.03.2007 | Mechanisms and Targets

MicroRNAs in the Search for Understanding Human Diseases

verfasst von: Dr Ranjan J. Perera, Animesh Ray

Erschienen in: BioDrugs | Ausgabe 2/2007

Einloggen, um Zugang zu erhalten

Abstract

MiroRNAs (miRNAs) are double-stranded, noncoding RNA molecules (with an average size of 22bp) that serve as post-transcriptional regulators of gene expression in higher eukaryotes. miRNAs play an important role in development and other cellular processes by hybridizing with complementary target mRNA transcripts, preventing their translation and thereby destabilizing the target transcripts. Though hundreds of miRNAs have been discovered in a variety of organisms, little is known about their cellular function. They have been implicated in the regulation of developmental timing and pattern formation, restriction of differentiation potential, regulation of insulin secretion, resistance to viral infection, and in genomic rearrangements associated with carcinogenesis or other genetic disorders, such as fragile X syndrome. Recent evidence suggests that the number of unique miRNA genes in humans exceeds 1000, and may be as high as 20 000. It is estimated that 20–30% of all human mRNAs are miRNA targets.
During the last few years, special attention has been given to miRNAs as candidate drug targets for cancer, diabetes mellitus, obesity, and viral diseases.
Literatur
1.
Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 2003; 113(6): 673–6PubMedCrossRef
2.
Bartel B, Bartel DP. MicroRNAs: at the root of plant development? Plant Physiol 2003; 132(2): 709–17PubMedCrossRef
3.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281–97PubMedCrossRef
4.
Pasquinelli AE, Reinhart BJ, Slack F, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000; 408(6808): 86–9PubMedCrossRef
5.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843–54PubMedCrossRef
6.
Lakatos L, Csorba T, Pantaleo V, et al. Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors. EMBO J 2006; 25(12): 2768–80PubMedCrossRef
7.
Yu B, Chapman EJ, Yang Z, et al. Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis. FEBS Lett 2006; 580(13): 3117–20PubMedCrossRef
8.
Grey F, Antoniewicz A, Allen E, et al. Identification and characterization of human cytomegalovirus-encoded microRNAs. J Virol 2005; 79(18): 12095–9PubMedCrossRef
9.
Reinhart BJ, Weinstein EG, Rhoades MW, et al. MicroRNAs in plants. Genes Dev 2002; 16(13): 1616–26PubMedCrossRef
10.
Lai EC, Tomancak P, Williams RW, et al. Computational identification of Drosophila microRNA genes. Genome Biol 2003; 4(7): R42PubMedCrossRef
11.
Lim LP, Lau NC, Weinstein EG, et al. The microRNAs of Caenorhabditis elegans. Genes Dev 2003; 17(8): 991–1008PubMedCrossRef
12.
Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 2005; 37(7): 766–70PubMedCrossRef
13.
Berezikov E, Guryev V, van de Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell 2005; 120(1): 21–4PubMedCrossRef
14.
Tuccoli A, Poliseno L, Rainaldi G. miRNAs regulate miRNAs: coordinated transcriptional and post-transcriptional regulation. Cell Cycle 2006; 5 (21): Epub ahead of print
15.
Matzke M, Aufsatz W, Kanno T, et al. Genetic analysis of RNA-mediated transcriptional gene silencing. Biochim Biophys Acta 2004; 1677(1–3): 129–41PubMed
16.
Jia S, Noma K, Grewal SI. RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins. Science 2004; 304(5679): 1971–6PubMedCrossRef
17.
Martienssen R, Lippman Z, May B, et al. Transposons, tandem repeats, and the silencing of imprinted genes. Cold Spring Harb Symp Quant Biol 2004; 69: 371–9PubMedCrossRef
18.
Martienssen RA, Zaratiegui M, Goto DB. RNA interference and heterochromatin in the fission yeast Schizosaccharomyces pombe. Trends Genet 2005 Aug; 21(8): 450–6PubMedCrossRef
19.
Mette MF, Matzke AJ, Matzke MA. Resistance of RNA-mediated TGS to HC-Pro, a viral suppressor of PTGS, suggests alternative pathways for dsRNA processing. Curr Biol 2001 Jul 24; 11(14): 1119–23PubMedCrossRef
20.
Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 2002 Feb 14; 415(6873): 810–3PubMedCrossRef
21.
Noma K, Sugiyama T, Cam H, et al. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat Genet 2004 Nov; 36(11): 1174–80PubMedCrossRef
22.
Robins H, Li Y, Padgett RW. Incorporating structure to predict microRNA targets. Proc Natl Acad Sci U S A 2005; 102(11): 4006–9PubMedCrossRef
23.
24.
Hill AE, Hong JS, Wen H, et al. Micro-RNA-like effects of complete intronic sequences. Front Biosci 2006; 11: 1998–2006PubMedCrossRef
25.
26.
Ying SY, Lin SL. Intron-derived microRNAs: fine tuning of gene functions. Gene 2004; 342(1): 25–8PubMedCrossRef
27.
Ying SY, Lin SL. Current perspectives in intronic micro RNAs (miRNAs). J Biomed Sci 2006; 13(1): 5–15PubMedCrossRef
28.
Stole V, Samanta MP, Tongprasit W, et al. Identification of transcribed sequences in Arabidopsis thaliana by using high-resolution genome tiling arrays. Proc Natl Acad Sci U S A 2005; 102(12): 4453–8CrossRef
29.
Robins H, Press WH. Human microRNAs target a functionally distinct population of genes with AT-rich 3′ UTRs. Proc Natl Acad Sci U S A 2005; 102(43): 15557–62PubMedCrossRef
30.
Xie X, Lu J, Kulbokas EJ, et al. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 2005; 434(7031): 338–45PubMedCrossRef
31.
Jing Q, Huang S, Guth S, et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005; 120(5): 623–34PubMedCrossRef
32.
Ambros V, Lee RC, Lavanway A, et al. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol 2003; 13(10): 807–18PubMedCrossRef
33.
34.
Yang WJ, Yang DD, Na S, et al. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem 2005; 280(10): 9330–5PubMedCrossRef
35.
Lee YS, Nakahara K, Pham JW, et al. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 2004; 117(1): 69–81PubMedCrossRef
36.
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120(1): 15–20PubMedCrossRef
37.
Vella MC, Reinert K, Slack FJ. Architecture of a validated microRNA::target interaction. Chem Biol 2004; 11(12): 1619–23PubMedCrossRef
38.
Cullen BR. Transcription and processing of human microRNA precursors. Mol Cell 2004; 16(6): 861–5PubMedCrossRef
39.
Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004; 10(12): 1957–66PubMedCrossRef
40.
Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNAs. Genes Dev 2003; 17(4): 438–42PubMedCrossRef
41.
Zhang B, Pan X, Cobb GP, et al. Plant microRNA: a small regulatory molecule with big impact. Dev Biol 2006; 289(1): 3–16PubMedCrossRef
42.
Meyers BC, Souret FF, Lu C, et al. Sweating the small stuff: microRNA discovery in plants. Curr Opin Biotechnol 2006; 17(2): 139–46PubMedCrossRef
43.
Carrington JC, Ambros V. Role of microRNAs in plant and animal development. Science 2003; 301(5631): 336–8PubMedCrossRef
44.
45.
Pasquinelli AE, Ruvkun G. Control of developmental timing by micrornas and their targets. Annu Rev Cell Dev Biol 2002; 18: 495–513PubMedCrossRef
46.
47.
48.
Ideker T, Thorsson V, Ranish JA, et al. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 2001; 292(5518): 929–34PubMedCrossRef
49.
Hobert O. Common logic of transcription factor and microRNA action. Trends Biochem Sci 2004; 29(9): 462–8PubMedCrossRef
50.
Dieterich C, Grossmann S, Tanzer A, et al. Comparative promoter region analysis powered by CORG. BMC Genomics 2005; 6(1): 24PubMedCrossRef
51.
Scitz H, Royo H, Lin SP, et al. Imprinted small RNA genes. Biol Chem 2004; 385(10): 905–11
52.
Ronemus M, Martienssen R. RNA interference: methylation mystery. Nature 2005;433(7025): 472–3PubMedCrossRef
53.
Gyory I, Minarovits J. Epigenetic regulation of lymphoid specific gene sets. Biochem Cell Biol 2005; 83(3): 286–95PubMedCrossRef
54.
Bentwich I. A postulated role for microRNA in cellular differentiation. Faseb J 2005; 19(8): 875–9PubMedCrossRef
55.
Cheng LC, Tavazoie M, Doetsch F. Stem cells: from epigenetics to microRNAs. Neuron 2005; 46(3): 363–7PubMedCrossRef
56.
Cawley S, Bekiranov S, Ng HH, et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 2004 Feb 20; 116(4): 499–509PubMedCrossRef
57.
Kampa D, Cheng J, Kapranov P, et al. Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res 2004 Mar; 14(3): 331–42PubMedCrossRef
58.
Lall S, Grun D, Krek A, et al. A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol 2006; 16(5): 460–71PubMedCrossRef
59.
Rajewsky N. microRNA target predictions in animals. Nat Genet 2006; 38Suppl. 1 (6s): S8–S13PubMedCrossRef
60.
Calin GA, Croce CM. Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol 2006; 33(2): 167–73PubMedCrossRef
61.
Calin GA, Croce CM. MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 2006; 25(46): 6202–10PubMedCrossRef
62.
Jannot G, Simard MJ. Tumour-related microRNAs functions in Caenorhabditis elegans. Oncogene 2006; 25(46): 6197–201PubMedCrossRef
63.
Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 2006; 25(46): 6188–96PubMedCrossRef
64.
Jovanovic M, Hengartner MO. miRNAs and apoptosis: RNAs to die for. Oncogene 2006; 25(46): 6176–87PubMedCrossRef
65.
66.
Hutvagner G. MicroRNAs and cancer: issue summary. Oncogene 2006; 25(46): 6154–5CrossRef
67.
Osada H, Takahashi T. MicroRNAs in biological processes and carcinogenesis. Carcinogenesis 2007 Jan; 28(1): 2–12PubMedCrossRef
68.
Zhang L, Coukos G. MicroRNAs: a new insight into cancer genome. Cell Cycle 2006 Oct; 5(19): 2216–9PubMedCrossRef
69.
Saito Y, Jones PA. Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 2006 Oct; 5(19): 2220–2PubMedCrossRef
70.
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 2005; 102(39): 13944–9PubMedCrossRef
71.
Calin GA, Liu CG, Sevignani C, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A 2004; 101(32): 11755–60PubMedCrossRef
72.
Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005; 353(17): 1793–801PubMedCrossRef
73.
Sevignani C, Calin GA, Siracusa LD, et al. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 2006; 17(3): 189–202PubMedCrossRef
74.
Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006; 25(17): 2537–45PubMedCrossRef
75.
Lee EJ, Gusev Y, Jiang J, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer 2007 Mar; 120(5): 1046–54PubMedCrossRef
76.
Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 2006; 26(21): 8191–201PubMedCrossRef
77.
Sun Y, Koo S, White N, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 2004; 32(22): el88CrossRef
78.
Esau C, Kang X, Peralta E, et al. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 2004; 279(50): 52361–5PubMedCrossRef
79.
Poy MN, Eliasson L, Krutzfeldt J, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature 2004; 432(7014): 226–30PubMedCrossRef
80.
Krutzfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab 2006; 4(1): 9–12PubMedCrossRef
81.
Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 2005; 436(7048): 214–20PubMedCrossRef
82.
van Rooij E, Sutherland LB, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A 2006; 103(48): 18255–60PubMedCrossRef
83.
Cao X, Yeo G, Muotri AR, et al. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 2006; 29: 77–103PubMedCrossRef
84.
Bilen J, Liu N, Burnett BG, et al. MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol Cell 2006; 24(1): 157–63PubMedCrossRef
85.
Jopling CL, Yi M, Lancaster AM, et al. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005 Sep 2; 309(5740): 1577–81PubMedCrossRef
86.
Zhang J, Yamada O, Sakamoto T, et al. Inhibition of hepatitis C virus replication by pol Ill-directed overexpression of RNA decoys corresponding to stem-loop structures in the NS5B coding region. Virology 2005; 342(2): 276–85PubMedCrossRef
87.
Bennasser Y, Le SY, Yeung ML, et al. MicroRNAs in human immunodeficiency virus-1 infection. Methods Mol Biol 2006; 342: 241–53
88.
Cullen BR. Is RNA interference involved in intrinsic antiviral immunity in mammals? Nat Immunol 2006; 7(6): 563–7PubMedCrossRef
89.
Berezikov E, Thuemmler F, van Laake LW, et al. Diversity of microRNAs in human and chimpanzee brain. Nat Genet 2006; 38(12): 1375–7PubMedCrossRef
Metadaten
Titel
MicroRNAs in the Search for Understanding Human Diseases
verfasst von
Dr Ranjan J. Perera
Animesh Ray
Publikationsdatum
01.03.2007
Verlag
Springer International Publishing
Erschienen in
BioDrugs / Ausgabe 2/2007
Print ISSN: 1173-8804
Elektronische ISSN: 1179-190X
DOI
https://doi.org/10.2165/00063030-200721020-00004

Weitere Artikel der Ausgabe 2/2007

BioDrugs 2/2007 Zur Ausgabe

Current Opinion

Ethics and Embryonic Stem Cell Research

Adis Drug Profile

Adalimumab in Crohn’s Disease

Current Opinion

HER-2-Positive Breast Cancer

Adis Profile Report

Panitumumab in the Treatment of Metastatic Colorectal Cancer

Adis Drug Profile

Adalimumab in Crohn’s Disease

Adis Drug Profile

Adalimumab