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RNA export to the cytoplasm: model systems

RNA maturation, transport & localization. RNA degradation. RNA export to the cytoplasm: model systems. RNA localization in the cytoplasm. Balbiani Rings (Chironomus tentans). BR RNP maturation. BR RNP translocation. BR RNP translocation. SUMMARY

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RNA export to the cytoplasm: model systems

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  1. RNA maturation, transport & localization RNA degradation RNA export to the cytoplasm: model systems RNA localization in the cytoplasm

  2. Balbiani Rings (Chironomus tentans)

  3. BR RNP maturation

  4. BR RNP translocation

  5. BR RNP translocation

  6. SUMMARY I. Multiple steps of mRNA biosynthesis are tightly coupled II. Mex67/TAP is one major mRNA export factor Binding to mRNA may already occur at the site of transcription III. Many questions remain - How are mRNA substrates released in the cytoplasm? - Are there multiple mRNA export pathways? - How is processing and transport coupled? etc.

  7. RNA half-lives vary greatly

  8. AUUUA element regulates half-life

  9. A. + 30,000 mRNA/cell B. Casein mRNA prolactin No change in transcription - 300 mRNA/cell

  10. mRNA DEGRADATION mRNA DECAY NMD ‘turnover’ ‘surveillance’

  11. mRNA DECAY AAAAAAAAAAAAAAAA m7Gppp poly A shortening Deadenylase complex AAA m7Gppp Decapitation Decapping enzyme (DCP1 complex) AAA 5’-3’ exonucleolytic cleavage Xrn1 complex

  12. From Neu-Yilik et al. (2001) EMBO 20:532-540

  13. Nonsense Mediated Decay Stop in penultimate exon/ 5’ of splicing mark m7Gppp AAAAAAAAAAAAAAAA Decapitation Decapping enzyme (DCP1 complex) AAAAAAAAAAAAAAAA 5’-3’ exonucleolytic cleavage Xrn1 complex

  14. RNA localization mRNA can be localized to subcellular compartments by actin or tubulin-dependent processes Examples: Xenopus: Vg1 mRNA (TGFb) to vegetal pole Drosophila: nanos, oskar mRNA (posterior) and bicoid (anterior) (requires mRNA binding protein staufen) prospero (into ganglion of mother cells; neuroblast TF) (requires staufen and miranda) Yeast: Ash1 mRNA to daughter cell

  15. lamellipodia staining perinuclear staining in myotubes

  16. Bertrand et al., Mol Cell (98) 2:437-445

  17. SUMMARY 2 I. mRNA decay - regulated and non-regulated turn-over - ordered pathway (deadenylation, decapping, exonucleolytic degradation) - NMD: recognition of premature stop codons II. Cytoplasmic mRNA localization - ZIP code in 3’ UTR - both actin and tubulin-mediated - yeast mating type switch as a model: Ash1 mRNA localization (via 3’ UTR, She2/3, Myo4 and actin cables)

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