Prachi Srivastava AMITY Institute of Biotechnology AMITY University Uttar Pradesh Lucknow Lucknow UP India introduction 2 RNA interference RNAi RNA interference RNAi is a highly evolutionally conserved process of posttranscriptional gene silencing PTGS ID: 1047228
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1. Regulatory Relationship of microRNAs in Alzheimer and Huntington Diseases: A Cladistics ApproachPrachi Srivastava AMITY Institute of Biotechnology AMITY University Uttar Pradesh Lucknow Lucknow, UP, India
2. introduction2
3. RNA interference (RNAi)RNA interference (RNAi) is a highly evolutionally conserved process of post-transcriptional gene silencing (PTGS) double stranded RNA (dsRNA), when introduced into a cell, causes sequence-specific degradation of homogolous mRNA sequences. It was first discovered in 1998 by Andrew Fire and Craig Mello in the nematode worm Caenorhabditis elegans and later found in a wide variety of organisms, including mammals
4. Timeline199819992000200120021990cosuppression of purple color in plantsdsRNA injection in wormsshort RNAs identified in plantsRNAi shown in vitroRISC activity partially purifiedsiRNAs identifiedDicer identifiedRNAi used against HIVgenome-wide RNAi screens begin
5. RNA InterferencePhenomena first observed in petuniaAttempted to overexpress chalone synthase (anthrocyanin pigment gene) in petunia. (trying to darken flower color) Caused the loss of pigment.Called co-suppression because suppressed expression of both endogenous gene and transgene
6. RNA Interference ApproachesFour types of responses induced by dsRNA6
7. The Mechanism of RNAi7
8. MicroRNA(miRNA)8
9. miRNA vs. siRNA9
10. Integration of RNAi in Drug Discovery 10
11. RNAi based therapeutics11
12. RNA-interference-based therapies12
13. 13
14. methodology14
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20. result and conclusion20
21. Alzheimer and Huntington 21
22. Alzheimer and Huntington S no.miRNAGene familyRegulation patternBootstrap score1.Mir-22(H)MIPF0000053Down Regulated10Mir-22(A)2.Mir-330(H)MIPF0000200Up Regulated5.17Mir-34a(A)MIPF0000039Down Regulated3.Mir-132(H)MIPF0000065Down Regulated5.00Mir-298(A)MIPF0000206Down Regulated4.Mir-128-1(H)MIPF0000065Down Regulated10Mir-128-1(A)Up Regulated5.Mir-29a(H)MIPF0000009Up Regulated10Mir-29a(A)Down Regulated22
23. Alzheimer and Parkinson 23
24. Alzheimer and Parkinson S no.miRNAGene familyRegulation patternBootstrap score1.Mir-26a-1(P)MIPF0000043Down regulated10Mir-26b(A)2.Mir-184(P)MIPF0000059N/A-Mir-320(A)MIPF0000163Up regulated24
25. Parkinson and Huntington25
26. Parkinson and HuntingtonS no.miRNAGene familyRegulation patternBootstrap score1.Mir-184(P)MIPF0000059Down regulated10Mir-132(H)MIPF00000652.Mir-133(P)MIPF0000029Down regulated6Mir-128-1(H)MIPF000004826
27. CONCLUSIONPhylogenetic analysis of miRNA of Alzheimer and Huntington diseases gives insight into evolutionary relationship and reveals regulation of Mir-22, Mir 29a, and mir-128-1 in both diseases. Mir-22 shows down-regulation in Parkinson disease and Alzheimer disease while mir-128-1 and mir-29a shows the difference in their regulation patternIn Alzheimer disease mir-128-1 is up regulated while in Huntington disease it is down regulated. Mir-29a is up regulated in Huntington disease while in Alzheimer disease, it is down regulated. These findings illustrates the importance of miRNA research in Neurodegenerative diseases with reference to novel targets identification which can give a better lead in concern to protective or prophylective approaches.27
28. REFERENCESBartel DP. MicroRNAs: genomics, biogenesis, mechanism, and Function. Cell 2004;116:281–97. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005;123:631–40.Perron MP, Provost P. Protein components of the microRNA pathway and human diseases. Methods Mol Biol 2009;487:369–85.Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. MiRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2005;34:D140–4. Luciano DJ, Mirsky H, Vendetti NJ, Maas S. RNA editing of a miRNA precursor. RNA 2004;10:1174–7. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human microRNA targets. PLoS Biol 2004;2:e363. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005;433:769–73.Griffiths-Jones S, Saini HK, Van Dongen S, Enright AJ: miRBase: tools for microRNA genomics. Nucleic Acids Res 2008, 36:D154–8.Olena AF, Patton JG: Genomic organization of microRNAs. Journal of cellular physiology 2009, 222:540–545.Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H: Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 2005, 33:2697–2706Kozomara A, Griffiths-Jones S: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011, 39:D152–7. Felsenstein J: PHYLIP (phylogeny inference package), version 3.5 c. Distributed by the author 1993. Felsenstein J: Parsimony in systematics: biological and statistical issues. Annual review of ecology and systematics 1983, 14:313–333. Zhang R, Wang Y-Q, Su B: Molecular evolution of a primate-specific microRNA family. Mol Biol Evol 2008, 25:1493–1502. Altuvia, Y, Landgraf, P, Lithwick, G, Elefant, N, Pfeffer, S, Aravin, A et al. (2005). Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 33: 2697–2706.28
29. 29Thank you.