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1. Introduction
2. Related publications
3. Outline
4. RNA interference
5. Dogma
6. Can duplex RNA also recognize DNA?
7. agRNAs target the PRB transcription start site
8. agRNAs are duplex RNAs
9. agRNAs inhibit protein expression
10. Inhibiting gene expression by using agRNAs
11. The Argonaute protein (Ago)
12. Inhibiting Ago2 blocks agRNAs silencing
13. Synthetic RNAs can control promoter DNA
14. Gene activation by promoter-targeted RNAs
15. Structure activity analysis: unexpected results
16. Hypothesis: 'inactive' RNA can activate genes
17. Testing the hypothesis in MCF7 cells
18. An RNA activates PR expression in MCF7 cells
19. What is the activation mechanism?
20. Inactive RNAs are competitive inhibitors
21. Clinical development of duplex RNA
22. Conclusions: RNA-mediated gene activation
23. Noncoding RNAs as molecular targets
24. Two possible mechanisms for activation
25. Most of the human genome is transcribed
26. What is a gene? two views
27. Antisense transcript overlaps PR promoter
28. The RIP technique
29. agRNAs recruit AGO to an antisense transcript
30. Conclusions from published work
31. RNA complementary to sequences beyond 3'-UTR
32. The 3' end: two views
33. PR mRNA was insufficiently characterized
34. A PR transcript ending around 13037
35. Quantitative RT-PCR confirmation of the 3' end
36. 3'-RACE defined the 3' end of PR mRNA
37. 3' noncoding sense transcript
38. PR is silenced in T47D cells by 3' agRNA
39. 3' agRNA reduces PR mRNA and pre-mRNA levels
40. 3' agRNA effect on 3' and 5' noncoding transcripts
41. 3' silencing agRNA reduces Pol2 recruitment
42. Noncoding transcript has target sites for 3' agRNA
43. Inhibitory 3' agRNA recruits AGO2 protein
44. PR is activated in MCF7 cells by a 3' agRNA
45. 3' activating agRNA increases mRNA levels
46. 3' activating agRNAs increase Pol2 recruitment
47. Activating 3' agRNA recruits AGO protein
48. miRNAs complementary to gene promoters
49. Expanding the pool of candidate miRNAs
50. miRNAs complementary to the PR gene promoter
51. miRNA mimics inhibit PR protein expression
52. Inhibition of PR protein by miR-423-5p mimic
53. miR-423-5p mimic inhibits PR mRNA expression
54. Complementarity to regions downstream of PR
55. A step towards endogenous 3' agRNAs?
56. Inhibition by miR-193b mimic is dose dependent
57. Inhibition of PR mRNA and pre-mRNA expression
58. 3' agRNAs conclusions
59. agRNAs target seq. 100,000 bases distant
60. The DNA looping theory
61. Are 5' and 3' of the PR gene in close proximity?
62. Experiments with PR13580
63. Experiments with PR9
64. Experiments with PR13515
65. Experiments with PR11
66. 5' and 3' ncRNA are in a complex
67. Proposed model
68. Acknowledgements

Topics Covered

• RNA-mediated recognition of chromosomal DNA
• Gene silencing
• Gene activation
• Mechanism of recognition of promoter DNA sequences by duplex RNAs
• Recognition of sequences beyond the 3'-termini of genes by duplex RNAs

Links

Series:

• RNA Interference

Categories:

• Cell Biology
• Genetics & Epigenetics

Talk Citation

Corey, D. (2010, February 9). Activation of gene expression by double-stranded RNA [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 23, 2024, from https://doi.org/10.69645/ROPK1509.
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Publication History

• Published on February 9, 2010
• Archived on April 17, 2016

Financial Disclosures

• Prof. David Corey has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.