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Exploring the RNA World: The Role of microRNA in Gene Regulation and Beyond

Chapter 25 delves into the fascinating world of microRNA (miRNA), previously deemed "junk" DNA, now recognized as crucial regulators of gene expression. Highlighting key contributions from Andrew Fire and Craig Mello, Nobel Prize winners in 2006 for their work on RNA interference, we explore the epigenetic control pathways of miRNA. Mechanisms of miRNA biogenesis, from transcription by Pol II to Dicer cleavage, are discussed, alongside the implications of artificial RNAi tools like shRNA and siRNA for health and disease. The dynamic between DNA and RNA raises compelling questions about biological control.

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Exploring the RNA World: The Role of microRNA in Gene Regulation and Beyond

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Presentation Transcript

  1. Chapter 25 The RNA World

  2. microRNA • Previously thought to be “junk” DNA • Now determined to “code” for other RNA • ENCODE project • Andrew Fire and Craig Mello • Nobel Prize in 2006 for miRNA • Epigenetic control

  3. miRNA pathway • Pol II makes RNA transcript • Drosha and other proteins trim the long pri-miRNA • Exportin 5 takes pre-miRNA out of nucleus • Dicer cleaves loop and separates strands? • RISC carries guide strand and releases passenger strand (degraded) • Basepairing with mRNA causes • Silencing if perfect pairing • Knockdown if imperfect (3’ UTR)

  4. Other RNAi Mechanisms (compare)

  5. shRNA or siRNA • This is the same as miRNA, but man-made • Must be designed carefully • Must be less than 30 nt • Otherwise degraded by host imune system • Cannot have strong hairpin loop • Want complementary strand to bind to RISC • Need a viral vector (manufacturer of the RNA)

  6. Health and Disease • Can currently silence genes in cell culture • How to use them in organisms? • Targets, specificity? • Learning tools in animal models

  7. Final Thought • Is DNA in control, or is RNA in control? • RNA world hypothesis may never have gone away

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