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2002.09.17

Drosha. 2002.09.17. 121th Lab meeting. 석사 2 년 박 은 실. Lin-4, Let-7. 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.

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2002.09.17

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  1. Drosha 2002.09.17

  2. 121th Lab meeting 석사 2년 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. Examples of Metazoan miRNAs stem loops involving the mature miRNAs (red) The miRNAs* (blue) 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 miRNA siRNA • Specific precursor • bind to the target 3′ UTRs through imperfect complementarity at multiple • sites • sampled more randomly from long dsRNAs • form a perfect duplex with their targets at only one site

  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-4와 lin-14 • Let-7(worms), Bantam(flies), miR30 (mammal) – negatively regulate • mir-196 = animal에서 유일하게 그 target인 Hoxb8에서 base pairing이 perfect하여 mRNA의 destruction일으킴 • miR-172 = 유일하게 coding 영역에 존재하며 plant에서 유일하게 repressor로 작용

  12. C. elegans : 116 • C. briggsae : 50 • D. melanogaster : 78 • 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.

  14. In vitro processing of miRNA by Drosha

  15. AGO protein 2004.08.05

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