Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-26T19:56:29.873Z Has data issue: false hasContentIssue false
  • English
  • Français

Molecular medicine of microRNAs: structure, function and implications for diabetes

Published online by Cambridge University Press:  15 August 2008

Erica Hennessy  and
Lorraine O'Driscoll
Erica Hennessy
Affiliation:
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
Get access Rights & Permissions [Opens in a new window]

Abstract

MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19–28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic β-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e24
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Bartel, D.P. and Chen, C.Z. (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5, 396-400CrossRefGoogle ScholarPubMed
2Zamore, P.D. (2004) Plant RNAi: how a viral silencing suppressor inactivates siRNA. Curr Biol 14, R198-200CrossRefGoogle ScholarPubMed
3Kumar, A. (2008) RNA interference: a multifaceted innate antiviral defense. Retrovirology 5, 17CrossRefGoogle ScholarPubMed
4Lau, N.C. et al. (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858-862CrossRefGoogle Scholar
5He, L. et al. (2005) A microRNA polycistron as a potential human oncogene. Nature 435, 828-833CrossRefGoogle ScholarPubMed
6Bartel, D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297CrossRefGoogle ScholarPubMed
7Brennecke, J. et al. (2005) Principles of microRNA-target recognition. PLoS Biol 3, e85CrossRefGoogle ScholarPubMed
8Leung, A.K. and Sharp, P.A. (2007) microRNAs: a safeguard against turmoil? Cell 130, 581-585CrossRefGoogle ScholarPubMed
9Lim, L.P. et al. (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769-773CrossRefGoogle ScholarPubMed
10Lim, L.P. et al. (2003) Vertebrate microRNA genes. Science 299, 1540CrossRefGoogle ScholarPubMed
11Zamore, P.D. and Haley, B. (2005) Ribo-gnome: the big world of small RNAs. Science 309, 1519-1524CrossRefGoogle Scholar
12Rajewsky, N. (2006) microRNA target predictions in animals. Nat Genet 38 Suppl, S8-13CrossRefGoogle ScholarPubMed
13Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854CrossRefGoogle Scholar
14Ha, I., Wightman, B. and Ruvkun, G. (1996) A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes Dev 10, 3041-3050CrossRefGoogle ScholarPubMed
15Olsen, P.H. and Ambros, V. (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216, 671-680CrossRefGoogle ScholarPubMed
16Reinhart, B.J. et al. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906CrossRefGoogle ScholarPubMed
17Slack, F.J. et al. (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5, 659-669CrossRefGoogle Scholar
18Lin, S.Y. et al. (2003) The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev Cell 4, 639-650CrossRefGoogle Scholar
19Vella, M.C. et al. (2004) The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3′UTR. Genes Dev 18, 132-137CrossRefGoogle Scholar
20Takuno, S. and Innan, H. (2008) Evolution of complexity in miRNA-mediated gene regulation systems. Trends Genet 24, 56-59CrossRefGoogle ScholarPubMed
21Blow, M.J. et al. (2006) RNA editing of human microRNAs. Genome Biol 7, R27CrossRefGoogle ScholarPubMed
22Lee, Y. et al. (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23, 4051-4060CrossRefGoogle Scholar
23Borchert, G.M., Lanier, W. and Davidson, B.L. (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13, 1097-1101CrossRefGoogle Scholar
24Cai, X., Hagedorn, C.H. and Cullen, B.R. (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10, 1957-1966CrossRefGoogle ScholarPubMed
25Denli, A.M. et al. (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432, 231-235CrossRefGoogle ScholarPubMed
26Gregory, R.I. et al. (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235-240CrossRefGoogle ScholarPubMed
27Han, J. et al. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18, 3016-3027CrossRefGoogle ScholarPubMed
28Lee, Y. et al. (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419CrossRefGoogle ScholarPubMed
29Ruby, J.G., Jan, C.H. and Bartel, D.P. (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448, 83-86CrossRefGoogle ScholarPubMed
30Jiang, F. et al. (2005) Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev 19, 1674-1679CrossRefGoogle ScholarPubMed
31Chendrimada, T.P. et al. (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436, 740-744CrossRefGoogle ScholarPubMed
32Saito, K. et al. (2005) Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol 3, e235CrossRefGoogle ScholarPubMed
33Gregory, R.I. et al. (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123, 631-640CrossRefGoogle ScholarPubMed
34Maniataki, E. and Mourelatos, Z. (2005) A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes Dev 19, 2979-2990CrossRefGoogle ScholarPubMed
35Nykanen, A., Haley, B. and Zamore, P.D. (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107, 309-321CrossRefGoogle ScholarPubMed
36Cook, H.A. et al. (2004) The Drosophila SDE3 homolog armitage is required for oskar mRNA silencing and embryonic axis specification. Cell 116, 817-829CrossRefGoogle ScholarPubMed
37Mourelatos, Z. et al. (2002) miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 16, 720-728CrossRefGoogle ScholarPubMed
38Pillai, R.S., Artus, C.G. and Filipowicz, W. (2004) Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA 10, 1518-1525CrossRefGoogle ScholarPubMed
39Caudy, A.A. et al. (2002) Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev 16, 2491-2496CrossRefGoogle ScholarPubMed
40Caudy, A.A. et al. (2003) A micrococcal nuclease homologue in RNAi effector complexes. Nature 425, 411-414CrossRefGoogle ScholarPubMed
41Hwang, H.W., Wentzel, E.A. and Mendell, J.T. (2007) A hexanucleotide element directs microRNA nuclear import. Science 315, 97-100CrossRefGoogle ScholarPubMed
42Zeng, Y., Yi, R. and Cullen, B.R. (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A 100, 9779-9784CrossRefGoogle ScholarPubMed
43Bagga, S. et al. (2005) Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122, 553-563CrossRefGoogle Scholar
44Jing, Q. et al. (2005) Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120, 623-634CrossRefGoogle ScholarPubMed
45Giraldez, A.J. et al. (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79CrossRefGoogle ScholarPubMed
46Humphreys, D.T. et al. (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 102, 16961-16966CrossRefGoogle ScholarPubMed
47Wang, B. et al. (2006) Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell 22, 553-560CrossRefGoogle Scholar
48Mathonnet, G. et al. (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317, 1764-1767CrossRefGoogle ScholarPubMed
49Wakiyama, M. et al. (2007) Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev 21, 1857-1862CrossRefGoogle Scholar
50Pillai, R.S. et al. (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573-1576CrossRefGoogle ScholarPubMed
51Kiriakidou, M. et al. (2007) An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129, 1141-1151CrossRefGoogle ScholarPubMed
52Chendrimada, T.P. et al. (2007) MicroRNA silencing through RISC recruitment of eIF6. Nature 447, 823-828CrossRefGoogle ScholarPubMed
53Petersen, C.P. et al. (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21, 533-542CrossRefGoogle ScholarPubMed
54Seggerson, K., Tang, L. and Moss, E.G. (2002) Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Dev Biol 243, 215-225CrossRefGoogle ScholarPubMed
55Behm-Ansmant, I. et al. (2006) mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 20, 1885-1898CrossRefGoogle Scholar
56Sen, G.L. and Blau, H.M. (2005) Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 7, 633-636CrossRefGoogle ScholarPubMed
57Liu, J. et al. (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7, 719-723CrossRefGoogle Scholar
58Jakymiw, A. et al. (2005) Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol 7, 1267-1274CrossRefGoogle Scholar
59Meister, G. et al. (2005) Identification of novel argonaute-associated proteins. Curr Biol 15, 2149-2155CrossRefGoogle Scholar
60Parker, R. and Song, H. (2004) The enzymes and control of eukaryotic mRNA turnover. Nat Struct Mol Biol 11, 121-127CrossRefGoogle ScholarPubMed
61Pillai, R.S., Bhattacharyya, S.N. and Filipowicz, W. (2007) Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 17, 118-126CrossRefGoogle ScholarPubMed
62Schmitter, D. et al. (2006) Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells. Nucleic Acids Res 34, 4801-4815CrossRefGoogle Scholar
63Rehwinkel, J. et al. (2005) A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11, 1640-1647CrossRefGoogle ScholarPubMed
64Brengues, M., Teixeira, D. and Parker, R. (2005) Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310, 486-489CrossRefGoogle ScholarPubMed
65Vasudevan, S. and Steitz, J.A. (2007) AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 128, 1105-1118CrossRefGoogle ScholarPubMed
66Vasudevan, S., Tong, Y. and Steitz, J.A. (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318, 1931-1934CrossRefGoogle ScholarPubMed
67Vasudevan, S., Tong, Y. and Steitz, J.A. (2008) Cell-cycle control of microRNA-mediated translation regulation. Cell Cycle 7, 1545-1549CrossRefGoogle ScholarPubMed
68Jopling, C.L. et al. (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309, 1577-1581CrossRefGoogle ScholarPubMed
69Yoon, S. and De Micheli, G. (2006) Computational identification of microRNAs and their targets. Birth Defects Res C Embryo Today 78, 118-128CrossRefGoogle ScholarPubMed
70Bentwich, I. et al. (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37, 766-770CrossRefGoogle ScholarPubMed
71Kiriakidou, M. et al. (2004) A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18, 1165-1178CrossRefGoogle ScholarPubMed
72Lewis, B.P. et al. (2003) Prediction of mammalian microRNA targets. Cell 115, 787-798CrossRefGoogle ScholarPubMed
73Farh, K.K. et al. (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310, 1817-1821CrossRefGoogle ScholarPubMed
74Bentwich, I. (2005) Prediction and validation of microRNAs and their targets. FEBS Lett 579, 5904-5910CrossRefGoogle ScholarPubMed
75Stark, A. et al. (2005) Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123, 1133-1146CrossRefGoogle Scholar
76Sood, P. et al. (2006) Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci U S A 103, 2746-2751CrossRefGoogle ScholarPubMed
77Maziere, P. and Enright, A.J. (2007) Prediction of microRNA targets. Drug Discov Today 12, 452-458CrossRefGoogle Scholar
78Zilberstein, C.B. et al. (2006) A high-throughput approach for associating MicroRNAs with their activity conditions. J Comput Biol 13, 245-266CrossRefGoogle Scholar
79Berezikov, E., Cuppen, E. and Plasterk, R.H. (2006) Approaches to microRNA discovery. Nat Genet 38 Suppl, S2-7CrossRefGoogle ScholarPubMed
80Krichevsky, A.M. et al. (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9, 1274-1281CrossRefGoogle ScholarPubMed
81Babak, T. et al. (2004) Probing microRNAs with microarrays: tissue specificity and functional inference. RNA 10, 1813-1819CrossRefGoogle ScholarPubMed
82Barad, O. et al. (2004) MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 14, 2486-2494CrossRefGoogle ScholarPubMed
83Liu, C.G. et al. (2004) An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A 101, 9740-9744CrossRefGoogle Scholar
84Miska, E.A. et al. (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5, R68CrossRefGoogle ScholarPubMed
85Sun, Y. et al. (2004) Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 32, e188CrossRefGoogle ScholarPubMed
86Thomson, J.M. et al. (2004) A custom microarray platform for analysis of microRNA gene expression. Nat Methods 1, 47-53CrossRefGoogle ScholarPubMed
87Baskerville, S. and Bartel, D.P. (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11, 241-247CrossRefGoogle ScholarPubMed
88Monticelli, S. et al. (2005) MicroRNA profiling of the murine hematopoietic system. Genome Biol 6, R71CrossRefGoogle ScholarPubMed
89Shingara, J. et al. (2005) An optimized isolation and labeling platform for accurate microRNA expression profiling. RNA 11, 1461-1470CrossRefGoogle ScholarPubMed
90Wienholds, E. et al. (2005) MicroRNA expression in zebrafish embryonic development. Science 309, 310-311CrossRefGoogle ScholarPubMed
91Castoldi, M. et al. (2006) A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA 12, 913-920CrossRefGoogle ScholarPubMed
92Nelson, P.T. et al. (2004) Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods 1, 155-161CrossRefGoogle ScholarPubMed
93Lu, J. et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435, 834-838CrossRefGoogle ScholarPubMed
94Allawi, H.T. et al. (2004) Quantitation of MicroRNAs using a modified Invader assay. RNA 10, 1153-1161CrossRefGoogle Scholar
95Kim, V.N. and Nam, J.W. (2006) Genomics of microRNA. Trends Genet 22, 165-173CrossRefGoogle ScholarPubMed
96Krutzfeldt, J. et al. (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438, 685-689CrossRefGoogle ScholarPubMed
97Davis, S. et al. (2006) Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res 34, 2294-2304CrossRefGoogle ScholarPubMed
98Esau, C. et al. (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3, 87-98CrossRefGoogle ScholarPubMed
99Zhou, H., Huang, C. and Xia, X.G. (2008) A tightly regulated Pol III promoter for synthesis of miRNA genes in tandem. Biochim Biophys Acta, Apr 7 [Epub ahead of print]CrossRefGoogle ScholarPubMed
100Esau, C. et al. (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279, 52361-52365CrossRefGoogle ScholarPubMed
101Brennecke, J. et al. (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25-36CrossRefGoogle ScholarPubMed
102Krutzfeldt, J. and Stoffel, M. (2006) MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab 4, 9-12CrossRefGoogle ScholarPubMed
103Chen, C.Z. et al. (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83-86CrossRefGoogle ScholarPubMed
104Zhao, Y., Samal, E. and Srivastava, D. (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436, 214-220CrossRefGoogle ScholarPubMed
105Poy, M.N. et al. (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230CrossRefGoogle ScholarPubMed
106Carthew, R.W. (2006) Gene regulation by microRNAs. Curr Opin Genet Dev 16, 203-208CrossRefGoogle Scholar
107Harfe, B.D. et al. (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102, 10898-10903CrossRefGoogle Scholar
108Dostie, J. et al. (2003) Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 9, 180-186CrossRefGoogle ScholarPubMed
109Jin, P. et al. (2004) Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 7, 113-117CrossRefGoogle ScholarPubMed
110Abelson, J.F. et al. (2005) Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320CrossRefGoogle ScholarPubMed
111Schratt, G.M. et al. (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439, 283-289CrossRefGoogle ScholarPubMed
112Calin, G.A. et al. (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101, 2999-3004CrossRefGoogle ScholarPubMed
113Calin, G.A. et al. (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99, 15524-15529CrossRefGoogle ScholarPubMed
114Stilgenbauer, S. et al. (1998) Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma. Oncogene 16, 1891-1897CrossRefGoogle ScholarPubMed
115Johnson, S.M. et al. (2005) RAS is regulated by the let-7 microRNA family. Cell 120, 635-647CrossRefGoogle ScholarPubMed
116Costinean, S. et al. (2006) Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A 103, 7024-7029CrossRefGoogle Scholar
117Lecellier, C.H. et al. (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308, 557-560CrossRefGoogle ScholarPubMed
118Bennasser, Y. et al. (2005) Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity 22, 607-619CrossRefGoogle Scholar
119Sullivan, C.S. and Ganem, D. (2005) A virus-encoded inhibitor that blocks RNA interference in mammalian cells. J Virol 79, 7371-7379CrossRefGoogle ScholarPubMed
120Samols, M.A. et al. (2007) Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathog 3, e65CrossRefGoogle ScholarPubMed
121Sullivan, C.S. et al. (2005) SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 435, 682-686CrossRefGoogle ScholarPubMed
122Cullen, B.R. (2006) Is RNA interference involved in intrinsic antiviral immunity in mammals? Nat Immunol 7, 563-567CrossRefGoogle ScholarPubMed
123Pedersen, I.M. et al. (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449, 919-922CrossRefGoogle ScholarPubMed
124Nathan, D.M. (1993) Long-term complications of diabetes mellitus. N Engl J Med 328, 1676-1685CrossRefGoogle ScholarPubMed
125[No authors listed] (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329, 977-986CrossRefGoogle Scholar
126O'Driscoll, L., Gammell, P. and Clynes, M. (2004) Mechanisms associated with loss of glucose responsiveness in beta cells. Transplant Proc 36, 1159-1162CrossRefGoogle ScholarPubMed
127O'Driscoll, L. et al. (2006) Phenotypic and global gene expression profile changes between low passage and high passage MIN-6 cells. J Endocrinol 191, 665-676CrossRefGoogle ScholarPubMed
128Dowling, P. et al. (2006) Proteomic screening of glucose-responsive and glucose non-responsive MIN-6 beta cells reveals differential expression of proteins involved in protein folding, secretion and oxidative stress. Proteomics 6, 6578-6587CrossRefGoogle ScholarPubMed
129Abderrahmani, A. et al. (2006) Mechanisms controlling the expression of the components of the exocytotic apparatus under physiological and pathological conditions. Biochem Soc Trans 34, 696-700CrossRefGoogle ScholarPubMed
130Dunn, W. et al. (2005) Human cytomegalovirus expresses novel microRNAs during productive viral infection. Cell Microbiol 7, 1684-1695CrossRefGoogle Scholar
131Yamakuni, T. et al. (2002) V-1, a catecholamine biosynthesis regulatory protein, positively controls catecholamine secretion in PC12D cells. FEBS Lett 530, 94-98CrossRefGoogle ScholarPubMed
132Antonin, W., Riedel, D. and von Mollard, G.F. (2000) The SNARE Vti1a-beta is localized to small synaptic vesicles and participates in a novel SNARE complex. J Neurosci 20, 5724-5732CrossRefGoogle Scholar
133Taoka, M. et al. (2003) V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein. J Biol Chem 278, 5864-5870CrossRefGoogle ScholarPubMed
134Hammar, E.B. et al. (2005) Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. J Biol Chem 280, 30630-30637CrossRefGoogle Scholar
135Norlin, S., Ahlgren, U. and Edlund, H. (2005) Nuclear factor-{kappa}B activity in {beta}-cells is required for glucose-stimulated insulin secretion. Diabetes 54, 125-132CrossRefGoogle ScholarPubMed
136Krek, A. et al. (2005) Combinatorial microRNA target predictions. Nat Genet 37, 495-500CrossRefGoogle ScholarPubMed
137Kloosterman, W.P. et al. (2007) Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol 5, e203CrossRefGoogle ScholarPubMed
138Baroukh, N. et al. (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282, 19575-19588CrossRefGoogle ScholarPubMed
139Enright, A.J. et al. (2003) MicroRNA targets in Drosophila. Genome Biol 5, R1CrossRefGoogle ScholarPubMed
140Zhang, X. et al. (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A 102, 4459-4464CrossRefGoogle ScholarPubMed
141Wu, K.L. et al. (1997) Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene. Mol Cell Biol 17, 6002-6013CrossRefGoogle ScholarPubMed
142Lee, C.S. et al. (2002) Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. Diabetes 51, 2546-2551CrossRefGoogle ScholarPubMed
143Jonsson, J. et al. (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371, 606-609CrossRefGoogle ScholarPubMed
144Offield, M.F. et al. (1996) PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122, 983-995CrossRefGoogle ScholarPubMed
145Stoffers, D.A. et al. (1997) Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 15, 106-110CrossRefGoogle ScholarPubMed
146Lantz, K.A. et al. (2004) Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 114, 512-520CrossRefGoogle ScholarPubMed
147Meissner, T., Beinbrech, B. and Mayatepek, E. (1999) Congenital hyperinsulinism: molecular basis of a heterogeneous disease. Hum Mutat 13, 351-3613.0.CO;2-R>CrossRefGoogle ScholarPubMed
148Kasai, K. et al. (2005) Rab27a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation. J Clin Invest 115, 388-396CrossRefGoogle ScholarPubMed
149Lovis, P., Gattesco, S. and Regazzi, R. (2008) Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem 389, 305-312CrossRefGoogle ScholarPubMed
150Lagos-Quintana, M. et al. (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12, 735-739CrossRefGoogle ScholarPubMed
151Landgraf, P. et al. (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401-1414CrossRefGoogle ScholarPubMed
152Plaisance, V. et al. (2006) MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281, 26932-26942CrossRefGoogle ScholarPubMed
153Wang, J. et al. (1999) Novel rabphilin-3-like protein associates with insulin-containing granules in pancreatic beta cells. J Biol Chem 274, 28542-28548CrossRefGoogle ScholarPubMed
154Torii, S. et al. (2004) Rab27 effector granuphilin promotes the plasma membrane targeting of insulin granules via interaction with syntaxin 1a. J Biol Chem 279, 22532-22538CrossRefGoogle ScholarPubMed
155Gomi, H. et al. (2005) Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol 171, 99-109CrossRefGoogle Scholar
156Coppola, T. et al. (2002) Pancreatic beta-cell protein granuphilin binds Rab3 and Munc-18 and controls exocytosis. Mol Biol Cell 13, 1906-1915CrossRefGoogle Scholar
157Torii, S. et al. (2002) Granuphilin modulates the exocytosis of secretory granules through interaction with syntaxin 1a. Mol Cell Biol 22, 5518-5526CrossRefGoogle ScholarPubMed
158Schleicher, E.D. and Olgemoller, B. (1992) Glomerular changes in diabetes mellitus. Eur J Clin Chem Clin Biochem 30, 635-640Google ScholarPubMed
159Ziyadeh, F.N. (1993) The extracellular matrix in diabetic nephropathy. Am J Kidney Dis 22, 736-744CrossRefGoogle ScholarPubMed
160Reeves, W.B. and Andreoli, T.E. (2000) Transforming growth factor beta contributes to progressive diabetic nephropathy. Proc Natl Acad Sci U S A 97, 7667-7669CrossRefGoogle Scholar
161Sharma, K. and Ziyadeh, F.N. (1995) Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes 44, 1139-1146CrossRefGoogle Scholar
162Poncelet, A.C. and Schnaper, H.W. (2001) Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells. J Biol Chem 276, 6983-6992CrossRefGoogle ScholarPubMed
163Tsuchida, K. et al. (2003) Role of Smad4 on TGF-beta-induced extracellular matrix stimulation in mesangial cells. Kidney Int 63, 2000-2009CrossRefGoogle ScholarPubMed
164Chin, B.Y. et al. (2001) Stimulation of pro-alpha(1)(I) collagen by TGF-beta(1) in mesangial cells: role of the p38 MAPK pathway. Am J Physiol Renal Physiol 280, F495-504CrossRefGoogle Scholar
165Hayashida, T. et al. (1999) TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression. Kidney Int 56, 1710-1720CrossRefGoogle ScholarPubMed
166Kato, M. et al. (2007) MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A 104, 3432-3437CrossRefGoogle ScholarPubMed
167Postigo, A.A. (2003) Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway. EMBO J 22, 2443-2452CrossRefGoogle ScholarPubMed
168Liu, S. et al. (2005) ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta1 stimulated glomerular podocytes. Cell Physiol Biochem 16, 207-216CrossRefGoogle ScholarPubMed
169Donnelly, R. et al. (2000) ABC of arterial and venous disease: vascular complications of diabetes. BMJ 320, 1062-1066CrossRefGoogle ScholarPubMed
170Duncan, C. et al. (1992) An audit of non-insulin-dependent diabetics attending a district general hospital diabetic clinic: implications for shared care between hospital and general practice. Health Bull (Edinb) 50, 302-308Google ScholarPubMed
171Casis, O. and Echevarria, E. (2004) Diabetic cardiomyopathy: electromechanical cellular alterations. Curr Vasc Pharmacol 2, 237-248CrossRefGoogle ScholarPubMed
172Veglio, M., Chinaglia, A. and Cavallo-Perin, P. (2004) QT interval, cardiovascular risk factors and risk of death in diabetes. J Endocrinol Invest 27, 175-181CrossRefGoogle ScholarPubMed
173Zhang, Y. et al. (2007) Ionic mechanisms underlying abnormal QT prolongation and the associated arrhythmias in diabetic rabbits: a role of rapid delayed rectifier K+ current. Cell Physiol Biochem 19, 225-238CrossRefGoogle Scholar
174Zhang, Y. et al. (2006) Restoring depressed HERG K+ channel function as a mechanism for insulin treatment of abnormal QT prolongation and associated arrhythmias in diabetic rabbits. Am J Physiol Heart Circ Physiol 291, H1446-1455CrossRefGoogle ScholarPubMed
175Xiao, J. et al. (2007) MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J Biol Chem 282, 12363-12367CrossRefGoogle ScholarPubMed
176Chen, J.F. et al. (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38, 228-233CrossRefGoogle Scholar
177Luo, X. et al. (2007) Transcriptional activation by stimulating protein 1 and post-transcriptional repression by muscle-specific microRNAs of IKs-encoding genes and potential implications in regional heterogeneity of their expressions. J Cell Physiol 212, 358-367CrossRefGoogle ScholarPubMed
178Esau, C.C. and Monia, B.P. (2007) Therapeutic potential for microRNAs. Adv Drug Deliv Rev 59, 101-114CrossRefGoogle ScholarPubMed
179He, A. et al. (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol 21, 2785-2794CrossRefGoogle ScholarPubMed
180Lynn, F.C. et al. (2007) MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes 56, 2983-2945CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Websites of the Computational Biology Center of the Memorial Sloan-Kettering Cancer Center, New York, USA, provide a range of bioinformatic tools, including a searchable database for predicted miRNA targets and expression:

http://cbio.mskcc.orgGoogle Scholar
http://www.microrna.org/microrna/home.doGoogle Scholar
http://microrna.sanger.ac.uk/sequences/Google Scholar
http://www.ambion.comGoogle Scholar