1. Biochemistry 430/530 Andrew MacMillan andrew.macmillan@ualberta.ca MedSci 4-39 (by appointment) 492-3813 http://www2.biochem.ualberta.ca/MacMillanLab/ “Course Notes”

2. Medicine/PhysiologyChemistry Szostak, Greider, Blackburn Steitz, Ramakrishnan, Yonath 1989 Sidney Altman, Thomas R. Cech 2006 Andrew Z. Fire, Craig C. Mello 1993 Richard J. Roberts, Phillip A. Sharp

4. Classical Gene Regulation

5. 1) RNA Structure/Reactivity (1) 2) Ribozymes/Riboswitches(2) 3) pre-mRNA Splicing (3) 4) RNA Degradation/RNAi(2)

6. RNA information function structure

7. Central Dogma

10. RNAi (siRNA, miRNA)

11. Hammerhead Ribozyme

12. Ribosome - Large Subunit H. marismortui Science (2000) 289:920-30 -2833 nt -27 proteins

13. Chemistry Review!

14. RNA Structure and Reactivity 1 2 3 4 5 6 7 8 9 3 2 1 6 5 4 1’ 2’ 3’ 4’ 5’

15. Nucleic Acids Chemical Functionalities -Hydrogen Bonding -Metal Coordination -Acid/Base -Nucleophilic Reactions

16. Hydrogen Bonding D A ~3-5 kcal/mol

17. Hydrogen Bonding D A ~3-5 kcal/mol (excluding entropy - how much is this worth?)

18. Metal Coordination Na +, K +, Mg 2+, Mn 2+

19. Acid/Base

20. pKa ~ 12 pKa ~ 14

21. Nucleophilic Reactions I

23. Nucleophilic Reactions II

24. B-Form DNA Dickerson and coworkers

25. A-Form RNA

26. Base-Pairing in RNA Watson-CrickHoogsteen

27. Base-Pairing in RNA Watson-CrickHoogsteen Major Minor

29. Higher Order Structure in Nucleic Acids From Non-WC Base-Pairs