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- RNAi-Pathway Components and Mechanisms
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1. Activation of gene expression by double-stranded RNAs
- Prof. Long-Cheng Li
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2. MicroRNA biogenesis
- Dr. Narry Kim
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3. Dicer and R2D2
- Dr. Young Sik Lee
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4. Mammalian microRNA assembly and function
- Prof. Zissimos Mourelatos
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5. Mechanisms of RNAi: a molecular view or Argonaute: the secret life of Slicer
- Prof. Leemor Joshua-Tor
- Roles for RNAi in Development and Anti-Viral Defense
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6. Functional roles of RNAi in C. elegans
- Dr. Eric Miska
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7. RNAi and heterochromatin in plants and fission yeast
- Prof. Robert Martienssen
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8. RNA interference functions and mechanisms in animals
- Prof. Richard Carthew
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9. Specific functional roles in mammals
- Dr. Michael McManus
- RNAi Design Rules for Applications in Humans
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10. siRNA on and off-target
- Prof. Anastasia Khvorova
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11. Cell signalling pathways and RNAi
- Mr. Michael O'Grady
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12. RNAi: key technological aspects
- Dr. Dmitry Samarsky
- Dr. Ciaran Faherty
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13. RNAi specificity: how big of an issue is it?
- Dr. Peter Welch
- Applications of RNAi in the Treatment of Human Diseases
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14. siRNA therapeutics
- Prof. John Rossi
- Mr. Daniel J. Rossi
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15. RNAi for neurological diseases
- Prof. Beverly L. Davidson
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16. RNA interference and cancer: a revolution?
- Dr. Annick Harel-Bellan
- Archived Lectures *These may not cover the latest advances in the field
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17. RNAi and viral heart infections
- Dr. Jens Kurreck
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18. RNA interference for neurodegenerative diseases
- Prof. Beverly L. Davidson
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19. Activation of gene expression by double-stranded RNA
- Prof. David Corey
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20. New designs for siRNAs as Dicer substrate
- Dr. Mark Behlke
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21. RNAi in the model system Drosophila
- Prof. Richard Carthew
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23. Therapeutic delivery of RNAi
- Dr. Patrick Lu
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24. Mechanistic aspects and therapeutic applications of RNAi
- Prof. John Rossi
Printable Handouts
Navigable Slide Index
- Introduction
- Related publications
- Outline
- RNA interference
- Dogma
- Can duplex RNA also recognize DNA?
- agRNAs target the PRB transcription start site
- agRNAs are duplex RNAs
- agRNAs inhibit protein expression
- Inhibiting gene expression by using agRNAs
- The Argonaute protein (Ago)
- Inhibiting Ago2 blocks agRNAs silencing
- Synthetic RNAs can control promoter DNA
- Gene activation by promoter-targeted RNAs
- Structure activity analysis: unexpected results
- Hypothesis: 'inactive' RNA can activate genes
- Testing the hypothesis in MCF7 cells
- An RNA activates PR expression in MCF7 cells
- What is the activation mechanism?
- Inactive RNAs are competitive inhibitors
- Clinical development of duplex RNA
- Conclusions: RNA-mediated gene activation
- Noncoding RNAs as molecular targets
- Two possible mechanisms for activation
- Most of the human genome is transcribed
- What is a gene? two views
- Antisense transcript overlaps PR promoter
- The RIP technique
- agRNAs recruit AGO to an antisense transcript
- Conclusions from published work
- RNA complementary to sequences beyond 3'-UTR
- The 3' end: two views
- PR mRNA was insufficiently characterized
- A PR transcript ending around 13037
- Quantitative RT-PCR confirmation of the 3' end
- 3'-RACE defined the 3' end of PR mRNA
- 3' noncoding sense transcript
- PR is silenced in T47D cells by 3' agRNA
- 3' agRNA reduces PR mRNA and pre-mRNA levels
- 3' agRNA effect on 3' and 5' noncoding transcripts
- 3' silencing agRNA reduces Pol2 recruitment
- Noncoding transcript has target sites for 3' agRNA
- Inhibitory 3' agRNA recruits AGO2 protein
- PR is activated in MCF7 cells by a 3' agRNA
- 3' activating agRNA increases mRNA levels
- 3' activating agRNAs increase Pol2 recruitment
- Activating 3' agRNA recruits AGO protein
- miRNAs complementary to gene promoters
- Expanding the pool of candidate miRNAs
- miRNAs complementary to the PR gene promoter
- miRNA mimics inhibit PR protein expression
- Inhibition of PR protein by miR-423-5p mimic
- miR-423-5p mimic inhibits PR mRNA expression
- Complementarity to regions downstream of PR
- A step towards endogenous 3' agRNAs?
- Inhibition by miR-193b mimic is dose dependent
- Inhibition of PR mRNA and pre-mRNA expression
- 3' agRNAs conclusions
- agRNAs target seq. 100,000 bases distant
- The DNA looping theory
- Are 5' and 3' of the PR gene in close proximity?
- Experiments with PR13580
- Experiments with PR9
- Experiments with PR13515
- Experiments with PR11
- 5' and 3' ncRNA are in a complex
- Proposed model
- 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
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 April 19, 2025, from https://doi.org/10.69645/ROPK1509.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. David Corey has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.