1. 2002.09.17 Drosha

2. 121th Lab meeting 석사 2 년 박 은 실

3. Lin-4, Let-7

4. What is RNAi ? A form of posttranscriptional gene silencing, in which dsRNA induces degradation of the homologous mRNA, mimicking the effect of the reduction, or loss, of gene activity. Kim VN., J Korean Med Sci. 2003

5. MicroRNA Small, Non coding RNAs 21~25nt long Negatively regulate gene expression Lin-4, Let-7 RNAse Ⅲ type enzyme Kim VN., J Korean Med Sci. 2003

6. stem loops involving the mature miRNAs (red) The miRNAs* (blue) Examples of Metazoan miRNAs David P. Bartel. cell. 2004

7. The molecular hallmarks of lin-4 Lin He and Gregory J.Hannon. Nature. 2004

8. MiRNAs and SiRNAs — what’s the difference terms of their molecular characteristics, biogenesis and effector functions share a common RNase-III processing enzyme, Dicer, and closely related effector complexes, RISCs, for post-transcriptional repression Specific precursor bind to the target 3′ UTRs through imperfect complementarity at multiple sites miRNA sampled more randomly from long dsRNAs form a perfect duplex with their targets at only one site siRNA

9. The current model for the biogenesis and post-transcriptional suppression Two processing First: nascent miRNA(pri- miRNA) → ~70nt precursor (pre-miRNA) Second: → 21~25nt mature miRNA Drosha, Dicer: ds RNA specific endonuclease Lin He and Gregory J.Hannon. Nature. 2004

10. The structure and function of the Dicer family Dicer1 and Dicer2 Deficiency in Dicer1 disrupts the processing of pre-miRNAs loss of Dicer2 affects the production of siRNAs, but not miRNA maturation. =PAZ domain is only present in Dicer1, but absent in Dicer2 Argonaute (AGO) proteins include PAZ domain and a piwi domain. Lin He and Gregory J.Hannon. Nature. 2004

11. Post-transcriptional repression by miRNAs Lin-4 와 lin-14 Let-7(worms), Bantam(flies), miR30 (mammal) – negatively regulate mir-196 = animal 에서 유일하게 그 target 인 Hoxb8 에서 base pairing 이 perfect 하여 mRNA 의 destruction 일으킴 miR-172 = 유일하게 coding 영역에 존재하 며 plant 에서 유일하게 repressor 로 작용

12. C. elegans : 116 C. briggsae : 50 D. melanogaster : 78 A.thaliana : 48 Rice : 28 Mouse : 207 Rat : 185 Human : 191

13. miR-26a and miR-99a expression is reduced in human lung cancer cell line.

15. In vitro processing of miRNA by Drosha

17. 2004.08.05 AGO protein