1 / 23

mRNA

mRNA. Cap Poly(A) tail Secondary structures IRES uORF Protein/RNA binding sites AUG Kozak consensus sequence: GCC( A / G )CC AUG G. Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004). Scanning model of Cap-dependent Translation Initiation. E.

corby
Download Presentation

mRNA

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. mRNA Cap Poly(A) tail Secondary structures IRES uORF Protein/RNA binding sites AUG Kozak consensus sequence: GCC(A/G)CCAUGG Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004)

  2. Scanning model of Cap-dependent Translation Initiation E P A eIF5B Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004) E P A

  3. http://departments.oxy.edu/biology/Stillman/bi221/091300/091300_lecture_figures.htmhttp://departments.oxy.edu/biology/Stillman/bi221/091300/091300_lecture_figures.htm

  4. Scanning model of Cap-dependent Translation Initiation E P A eIF5B Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004) E P A

  5. Translation of mRNAs in ∆eIF5B Yeast { Polysomes { Actin Northern

  6. Global Regulation

  7. Recycling of the ternary complex requires eIF2B Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004)

  8. eIF2 Phosphorylation Reduces Ternary Complex Starvation (GCN2) Viral infection, apoptisis (PKR) ER Stress (PERK) Haemin-regulated inhibitor (HRI) Fátima Gebauer & Matthias W. Hentze Nature Reviews Molecular Cell Biology 5, 827-835 (2004)

  9. uORFS 1 2 3 4 GCN4

  10. uORFs function in Gcn4 translational control

  11. GCN4: Non-starvation Starvation

  12. eIF4E binding proteins: 4E-BP Apoptosis Insulin AA (Leucine) Cell Proliferation

  13. SJ Morley, MJ Codwell, MJ Clemens (2006) Cell Death and Diff. 12, 571-584.

  14. Message specific regulation of translation initiation

  15. IRE/IRP: steric hindrance IRE-IRBP Thomson et al. (1999) Intnl. J. Biochem & cell Biol. 31, pp 1139-1152.

  16. Sex-lethal: SXL Ann-Bin Shyu. Nature Struct. & Molec. Biol. (2006) 13, 189-190.

  17. Viral IRES X&Y=> IRES Trans-acting factors Stoneley and Willis (2004) Oncogene 23, 3200-3207

  18. IRES Mechanisms of Internal Initiation IRES

  19. Dicistronic Assay for IRES acitivity

  20. Cap-Independent Translation Initiation • Cellular • Cellular stress: viral infection (PKR), apoptosis, hypoxia • Normal cellular processes: G2/M phase cell cycle • Viral • Genomes: Picornaviruses, Hepatitis C Virus, Cricket paralysis virus • Specific viral messages: HIV, Herpes virus (…. and the list is still growing!)

  21. Cellular IRESes: How do they recruit 40S? • Widely assumed that the Secondary and tertiary Structure allow for interactions with translational machinery (ITAF,eIFs, 40S) • No common Structure • Composed of multiple short modules • Generally 150-300 nts long, exception: 9nt repeated element.

  22. mRNA-rRNA base-pairing Dresios et al. (2006) Nature Struct.& Mol. Bio. 13, 30-34.

  23. Summary • Mechanisms of initiation: • Cap-dependent translation • Cap-independent translation: Internal ribosome entry sites • Regulation of initiation: • Global • eIF2 alpha phosphorylation • 4E-BPs • Cleavage of eIF4G • Message specific • GCN4 • IRE/IRP • SXL • miRNA (microRNA)

More Related