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Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region

Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region. Andrea B. Eberle, Lukas Stalder, Hansruedi Mathys, Rodolfo Zamudio Orozco, Oliver Mühlemann Charu Shukla 9/9/08. Nonsense Mediated mRNA Decay.

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Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region

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  1. Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region Andrea B. Eberle, Lukas Stalder, Hansruedi Mathys, Rodolfo Zamudio Orozco, Oliver Mühlemann Charu Shukla 9/9/08

  2. Nonsense Mediated mRNA Decay • A post transcriptional translation-dependent surveillance mechanism that prevents the synthesis of proteins carrying PTC • Transcripts with upstream open reading frame • Transcripts containing introns in the 3’ UTR • Transcripts derived from alternative splicing

  3. Simplified model of NMD. Nature Genetics  36, 801 - 808 (2004) Kulozik et al

  4. (I) 3’ UTR Extensions Reduce mRNA Half Life by NMD Distance b/w TC and poly(A) tail is crucial for NMD

  5. (2) Suppression Of EJC independent NMD by Poly(A) tail FB

  6. (3) mRNA stability depends on the distance b/w PTC and Poly(A) tail

  7. (4) Suppression of EJC-Enhanced NMD by poly(A) tail FB

  8. (5) Tethering PABPC1 near a PTC suppresses NMD

  9. Model for Posttranscriptional Gene Regualtion by spatial Rearrangement of 3’UTR

  10. A Competition between Stimulators and Antagonists of Upf Complex Recruitment Governs Human Nonsense-Mediated mRNA Decay Guramrit Singh, Indrani Rebbapragada, Jens Lykke-Andersen

  11. A 3’ UTR is not suffiecient to trigger NMD

  12. Intron-less extended 3’UTRs trigger NMD in human cells

  13. PABPC1 antagonizes NMD

  14. Normal Long 3’UTR an Evade NMD

  15. A 3’UTR Intron Enhances NMD

  16. PABC1 Antagonizes the interaction between eRF3 and hUpf1 in vitro

  17. A Competition between stimulators and antagonists of Upf Complex Recruitment in Human NMD

  18. Unified Model of NMD PTC recognition: • Competition between 3’ UTR associated factors stimulate or antagonize recruitment of Upf complex to the terminating ribosome

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