Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-19T05:54:42.831Z Has data issue: false hasContentIssue false
  • English
  • Français

MicroRNA Signatures in Neurological Disorders

Published online by Cambridge University Press:  02 December 2014

Gowhar Shafi ,
Nishat Aliya  and
Anjana Munshi
Gowhar Shafi
Affiliation:
Institute of Genetics & Hospital for Genetic Diseases, Begumpet Hyderabad-AP, India
Nishat Aliya
Affiliation:
Institute of Genetics & Hospital for Genetic Diseases, Begumpet Hyderabad-AP, India
Anjana Munshi*
Affiliation:
Institute of Genetics & Hospital for Genetic Diseases, Begumpet Hyderabad-AP, India
*
Institute of Genetics & Hospital for Genetic Diseases, Begumpet Hyderabad-500016, AP, India.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

A class of small, non-coding transcripts called microRNAs (miRNAs) that play a major role in post-transcriptional gene regulation has recently emerged and become the focus of intense research. MicroRNAs are abundant in the nervous system, where they have key roles in development and are likely to be important mediators of plasticity. A highly conserved pathway of miRNA biogenesis is closely linked to the transport and translatability of mRNAs in neurons. MicroRNAs have been shown to modulate programmed cell death during development. Although there are nearly 750 known human miRNA sequences, each of only approximately 20-25 nucleotides in length that bind to multiple mRNA targets, the accurate prediction of miRNA targets seems to lie just beyond our grasp. Nevertheless, the identification of such targets promises to provide new insights into many facets of neuronal function. In this review, we briefly describe miRNA biogenesis and the principle approaches for studying the function of miRNAs and potential application of miRNAs as biomarkers, diagnostic targets, and potential therapeutic tools of human diseases in general and neurological disorders in particular.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 2 , March 2010 , pp. 177 - 185
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. Ambros, V. MicroRNAs: tiny regulators with great potential. Cell. 2001;107:823–6.Google Scholar
2. Ambros, V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113(6):673–6.CrossRefGoogle ScholarPubMed
3. Bartel, DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefGoogle ScholarPubMed
4. Carrington, JC, Ambros, V. Role of microRNAs in plant and animal development. Science. 2003;301:336–8.CrossRefGoogle ScholarPubMed
5. Floyd, SK, Bowman, JL. Gene regulation: ancient microRNA target sequences in plants. Nature. 2004;428:485–6.Google Scholar
6. Ambros, V. The functions of animal microRNAs. Nature. 2004;431: 350–5.CrossRefGoogle ScholarPubMed
7. Lee, RC, Feinbaum, RL, Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.Google Scholar
8. Berezikov, E, Guryev, V, van de Belt, J, Wienholds, E, Plasterk, RH, Cuppen, E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120:21–4.Google Scholar
9. Lewis, BP, Burge, CB, Bartel, DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefGoogle ScholarPubMed
10. Markesbery, WR, Lovell, MA. Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Arch Neurol. 2007;64(7): 954–6.Google Scholar
11. Nelson, PT, Keller, JN. RNA in brain disease: no longer just “the messenger in the middle”. J Neuropathol Exp Neurol. 2007;6: 461–8.Google Scholar
12. Calin, GA, Liu, CG, Sevignani, C, Ferracin, M, Felli, N, Dumitru, CD, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA. 2004; 101:11755–60.Google Scholar
13. Kim, VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376–85.Google Scholar
14. Han, J, Lee, Y, Yeom, KH, Nam, JW, Heo, I, Rhee, JK, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006;125:887–901.Google Scholar
15. Lund, E, Guttinger, S, Calado, A, Dahlberg, JE, Kutay, U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.CrossRefGoogle ScholarPubMed
16. Bohnsack, MT, Czaplinski, K, Gorlich, D. Exportin 5 is a RanGTPdependent dsRNA-binding protein that mediates nuclear export of premiRNAs. RNA. 2004;10:185–91.Google Scholar
17. Yi, R, Qin, Y, Macara, IG, Cullen, BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011–16.Google Scholar
18. Chendrimada, TP, Gregory, RI, Kumaraswamy, E, Norman, J, Cooch, N, Nishikura, K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740–4.Google Scholar
19. Gregory, RI, Chendrimada, TP, Cooch, N, Shiekhattar, R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123:631–40.Google Scholar
20. Meister, G, Landthaler, M, Patkaniowska, A, Dorett, Y, Teng, G, Tuschl, T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15:185–97.Google Scholar
21. Hutvagner, G, Zamore, PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297:2056–60.CrossRefGoogle Scholar
22. Lagos-Quintana, M, Rauhut, R, Yalcin, A, Meyer, J, Lendeckel, W, Tuschl, T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12:735–9.Google Scholar
23. Kim, J, Krichevsky, A, Grad, Y, Hayes, GD, Kosik, KS, Church, GM, et al. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci. 2004;101:360–5.Google Scholar
24. Nelson, PT, Hatzigeorgiou, AG, Mourelatos, Z. miRNP:mRNA association in polyribosomes in a human neuronal cell line. RNA. 2004;10:387–94.CrossRefGoogle Scholar
25. Giraldez, AJ, Cinalli, RM, Glasner, ME, Enright, AJ, Thomson, JM, Baskerville, S, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308:833–8.CrossRefGoogle ScholarPubMed
26. Bernstein, E, Kim, SY, Carmell, MA, Murchison, EP, Alcorn, H, Li, MZ, et al. Dicer is essential for mouse development. Nat Genet. 2003;35:215–17.CrossRefGoogle ScholarPubMed
27. Schaefer, D, O’Carroll, CL, Tan, D, Hillman, M, Sugimori, R, Llinas, P, et al. Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med. 2007;204:1553–8.Google Scholar
28. Kim, J, Inoue, K, Ishii, J, Vanti, WB, Voronov, SV, Murchison, E, et al. A MicroRNA feedback circuit in midbrain dopamine neurons. Science. 2007;317:1220–4.Google Scholar
29. Bonhoeffer, T, Yuste, R. Spine motility: phenomenology, mechanisms, and function. Neuron. 2002;35:1019–27.Google Scholar
30. Kloosterman, WP, Plasterk, RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006; 11:441–50.Google Scholar
31. Chen, K, Rajewsky, N. Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet. 2006;38: 1452–6.Google Scholar
32. Abelson, JF, Kwan, KY, O’Roak, BJ, Baek, DY, Stillman, AA, Morgan, TM, et al. Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science. 2005;310:317–20.Google Scholar
33. Perkins, DO, Jeffries, CD, Jarskog, LF, Thomson, JM, Woods, K, Newman, MA, et al. MicroRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol. 2007;8:R27.Google Scholar
34. Hansen, T, Olsen, L, Lindow, M, Jakobsen, KD, Ullum, H, Jonsson, E, et al. Brain expressed microRNAs implicated in schizophrenia etiology. PLoS ONE. 2007;2:e873.Google Scholar
35. Bilen, J, Liu, N, Burnett, BG, Pittman, RN, Bonini, NM. MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol Cell. 2006;24:157–63.Google Scholar
36. Garzon, R, Fabbri, M, Cimmino, A, Calin, GA, Croce, CM. MicroRNA expression and function in cancer. Trends Mol Med. 2006;12: 580–7.CrossRefGoogle ScholarPubMed
37. Ciafre, SA, Galardi, S, Mangiola, A, Ferracin, M, Liu, CG, Sabatino, G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334: 1351–8.CrossRefGoogle ScholarPubMed
38. Chan, JA, Krichevsky, AM, Kosik, KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.Google Scholar
39. Sathyan, P, Golden, HB, Miranda, RC. Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. J Neurosci. 2007;27:8546–57.Google Scholar
40. Martin, KC, Kosik, KS. Synaptic tagging-who’s it? Nat Rev Neurosci. 2002;3:813–20.Google Scholar
41. Jeyaseelan, K, Lim, KY, Armugam, A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008;39:959–66.CrossRefGoogle ScholarPubMed
42. Zhao, Y, Samal, E, Srivastava, D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005;436:214–20.Google Scholar
43. Johnston, RJ, Hobert, OA. MicroRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003;426:845–9.Google Scholar
44. Chang, S, Johnston, RJ, Frokjaer-Jensen, C, Lockery, S, Hobert, O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature. 2004;430: 785–9.Google Scholar
45. Vo, N, Klein, ME, Varlamova, O, Keller, DM, Yamamoto, T, Goodman, RH, et al. cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci USA. 2005;102:16426–31.CrossRefGoogle ScholarPubMed
46. Krichevsky, AM, King, KS, Donahue, CP, Khrapko, K, Kosik, KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 2003;9:1274–81.Google Scholar
47. Jin, P, Alisch, RS, Warren, ST. RNA and microRNAs in fragile X mental retardation. Nat Cell Biol. 2004;6:1048–53.Google Scholar
48. Sempere, LF, Freemantle, S, Pitha-Rowe, I, Moss, E, Dmitrovsky, E, Ambros, V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004;5:R13.Google Scholar
49. Cheng, LC, Tavazoie, M, Doetsch, F. Stem cells: from epigenetics to microRNAs. Neuron. 2005;46:363–7.Google Scholar
50. Kosik, KS, Krichevsky, AM. The elegance of the microRNAs: a neuronal perspective. Neuron. 2005;47:779–82.CrossRefGoogle ScholarPubMed
51. Smirnova, L, Grafe, A, Seiler, A, Schumacher, S, Nitsch, R, Wulczyn, FG. Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 2005;21:1469–77.CrossRefGoogle ScholarPubMed
52. Conaco, C, Otto, S, Han, JJ, Mandel, G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci USA. 2006;103:2422–7.Google Scholar
53. Schratt, GM, Tuebing, F, Nigh, EA, Kane, CG, Sabatini, ME, Kiebler, M, et al. A brain-specific microRNA regulates dendritic spine development. Nature. 2006;439:283–9.CrossRefGoogle ScholarPubMed
54. Schaeffer, C, Beaulande, M, Ehresmann, C, Ehresmann, B, Moine, H. The RNA binding protein FMRP: new connections and missing links. Biol Cell. 2003;95:221–8.CrossRefGoogle ScholarPubMed
55. Lugli, G, Larson, J, Martone, ME, Jones, Y, Smalheiser, NR. Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. J Neurochem. 2005;94:896–905.Google Scholar
56. Ashraf, SI, McLoon, AL, Sclarsic, SM, Kunes, S. Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell. 2006;124:191–205.Google Scholar
57. John, B, Enright, AJ, Aravin, A, Tuschl, T, Sander, C, Marks, DS. Human microRNA targets. PLoS Biol. 2004;2:e363.Google Scholar
58. Krützfeldt, J, Poy, MN, Stoffel, M. Strategies to determine the biological function of microRNAs. Nat Genet. 2006;38:S14.Google Scholar
59. Baskerville, S, Bartel, DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005;11:241–7.Google Scholar
60. Liu, J, Michelle, AC, Fabiola, VR, Carolyn, GM, Michael, JT, Ji-Joon, S, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Sci. 2004;305:1437–41.Google Scholar
61. Wang, H, Ach, RA, Curry, B. Direct and sensitive miRNA profiling from low-input total RNA. RNA. 2007;13:151–9.Google Scholar
62. Schmittgen, TD, Jiang, JM, Liu, Q, Yang, LQ. A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 2004;32:e48.Google Scholar
63. Vidal, L, Blagden, S, Attard, G, de Bono, J. Making sense of antisense. Eur J Cancer. 2005;41:2812–18.Google Scholar
64. Jackson, AL, Burchard, J, Schelter, J, Chau, BN, Cleary, M, Lim, L, et al. Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity. RNA. 2006;12: 1179–87.Google Scholar
65. Birmingham, A, Anderson, EM, Reynolds, A, Ilsley-Tyree, D, Leake, D, Edorov, Y, et al. 3’ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat Methods. 2006;3: 199–204.Google Scholar
66. Fedorov, Y, Anderson, EM, Birmingham, A, Reynolds, A, Karpilow, J, Obinson, K, et al. A. Off-target effects by siRNA can induce toxic phenotype. RNA. 2006;12:1188–96.CrossRefGoogle ScholarPubMed
67. Grimm, D, Streetz, KL, Jopling, CL, Storm, TA, Pandey, K, Davis, CR, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006;441: 537–41.Google Scholar
68. Soifer, HS, Rossi, JJ, Saetrom, P. MicroRNAs in disease and potential therapeutic applications. Mol Ther. 2007;15(12):2070–9.Google Scholar
69. Davis, S, Lollo, B, Freier, S, Esau, C. Improved targeting of miRNA with antisense oligonucleotides. Nucl Acids Res. 2006;34: 2294–304.Google Scholar
70. Wurdinger, T, Costa, FF. Molecular therapy in the microRNA era. Pharmacogenomics J. 2007;7:297–304.Google Scholar
71. Meister, G, Landthaler, M, Dorsett, Y, Tuschl, T. Sequence-specific inhibition of microRNA and siRNA-induced RNA silencing. RNA. 2004;10:544–50.CrossRefGoogle ScholarPubMed
72. Hutvagner, G, Simard, MJ, Mello, CC, Zamore, PD. Sequencespecific inhibition of small RNA function. PLoS Biol. 2004; 2:E98.Google Scholar
73. Boutla, A, Delidakis, C, Tabler, M. Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Nucl Acids Res. 2003;31:4973–80.Google Scholar
74. Orom, UA, Kauppinen, S, Lund, AH. LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene. 2006;372:137–41.Google Scholar
75. Leaman, D, Chen, PY, Fak, J, Yalcin, A, Pearce, M, Unnerstall, U. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell. 2005; 121:1097–108.Google Scholar
76. Esau, C, Davis, S, Murray, SF, Yu, XX, Pandey, SK, Pear, M. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3:87–98.Google Scholar
77. Krutzfeldt, J, Kuwajima, S, Braich, R, Rajeev, KG, Pena, J, Tuschl, T, et al. Specificity, duplex degradation and subcellular localization of antagomirs. Nucl Acids Res. 2007; 35:2885–92.Google Scholar
78. Rodriguez-Lebron, E, Paulson, HL. Allele-specific RNAinterference for neurological disease. Gene Ther. 2006;13:576–81.Google Scholar
79. Houbaviy, HB, Murray, MF, Sharp, PA. Embryonic stem cell-specific microRNAs. Dev Cell. 2003;5:351–8.Google Scholar
80. Suh, MR, Lee, Y, Kim, JY, Kim, SK, Moon, SH, Lee, JY, et al. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 2004;270:488–98.Google Scholar
81. Forstemann, K, Tomari, Y, Du, TT, Vagin, VV, Denli, AM, Bratu, DP, et al. Normal microRNA maturation and germline stem cell maintenance requires loquacious, a double-stranded RNA binding domain protein. Plos Biol. 2005;3:1187–201.Google Scholar
82. Hatfield, SD, Shcherbata, HR, Fischer, KA, Nakahara, K, Carthew, RW, Ruohola-Baker, H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435:974–8.Google Scholar
83. Kanellopoulou, C, Muljo, SA, Kung, AL, Ganesan, S, Drapkin, R, Jenuwein, T, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 2005;19:489–501.Google Scholar
84. Lancman, JJ, Caruccio, NC, Harfe, BD, Pasquinelli, AE, Schageman, JJ, Pertsemlidis, A, et al. Analysis of the regulation of lin-41 during chick and mouse limb development. Dev Dyn. 2005;234: 948–60.Google Scholar
85. Lee, YS, Kim, HK, Chung, S, Kim, KS, Dutta, A. Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the downregulation of putative targets during differentiation. J Biol Chem. 2005;280:16635–41.Google Scholar
86. Murchison, EP, Partridge, JF, Tam, OH, Cheloufi, S, Hannon, GJ. Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA. 2005;102:12135–40.Google Scholar
87. Krichevsky, AM, King, KS, Donahue, CP, Khrapko, K, Kosik, KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 2003;9:1274–81.CrossRefGoogle ScholarPubMed
88. Miska, EA, Alvarez-Saavedra, E, Townsend, M, Yoshii, A, Sestan, N, Rakic, P, et al. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol. 2004;5:R68.Google Scholar
89. Rogelj, B, Giese, KP. Expression and function of brain specific small RNAs. Rev Neurosci. 2004;15:185–98.Google Scholar
90. Giraldez, AJ, Cinalli, RM, Glasner, ME, Enright, AJ, Thomson, JM, Baskerville, S, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308:833–8.Google Scholar
91. Rogaev, EI. Small RNAs in human brain development and disorders. Biochemistry(Mos). 2005;70:1404–7.Google Scholar
92. Rowan, A. Development—MicroRNAs and brain morphogenesis. Nature Rev Neurosci. 2005;6:499.Google Scholar
93. Wu, LG, Belasco, JG. Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Mol Cell Biol. 2005;25:9198–208.Google Scholar
94. Schratt, GM, Tuebing, F, Nigh, EA, Kane, CG, Sabatini, ME, Kiebler, M, et al. A brain-specific microRNA regulates dendritic spine development. Nature. 2006;439:283–9.Google Scholar
95. Kloosterman, WP, Wienholds, E, Ketting, RF, Plasterk, RHA. Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res. 2004;32:6284–91.Google Scholar
96. Aboobaker, AA, Tomancak, P, Patel, N, Rubin, GM, Lai, EC. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci USA. 2005;102:18017–22.Google Scholar
97. Yang, WJ, Yang, DD, Na, SQ, Sandusky, GE, Zhang, Q, Zhao, GS. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem. 2005;280:9330–5.Google Scholar
98. Schubert, C. MicroRNAs manage the heart. Nature Med. 2005; 11:714.Google Scholar
99. Zhao, Y, Samal, E, Srivastava, D. Serum, response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Circulation. 2005;112:U107.Google Scholar
100. Maatouk, DM, McManus, MT, Harfe, BD. MicroRNA regulation of murine limb development. Dev Biol. 2005;283:698.Google Scholar
101. Lamb, J, Crawford, ED, Peck, D, Modell, JD, Blat, IC, Wrobel, MJ, et al. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006; 313:1929–35.CrossRefGoogle ScholarPubMed
102. Lin, He, Xingyue, He, Lowe, SW, Hannom, GJ. MicroRNAs join the p53 network - another piece in the tumor- suppression puzzle. Nature Reviews Cancer. 2007;7:819–22.Google Scholar