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-Structure paper
| Title | Intracellular pathogen effector reprograms host gene expression by inhibiting mRNA decay. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 6452, Year 2025 |
| Publish date | Jul 12, 2025 |
Authors | Yevgen Levdansky / Justin C Deme / David J Turner / Claire T Piczak / Filip Pekovic / Anna L Valkov / Sergey G Tarasov / Susan M Lea / Eugene Valkov / ![]() |
| PubMed Abstract | Legionella pneumophila, an intracellular bacterial pathogen, injects effector proteins into host cells to manipulate cellular processes and promote its survival and proliferation. Here, we reveal a ...Legionella pneumophila, an intracellular bacterial pathogen, injects effector proteins into host cells to manipulate cellular processes and promote its survival and proliferation. Here, we reveal a unique mechanism by which the Legionella effector PieF perturbs host mRNA decay by targeting the human CCR4-NOT deadenylase complex. High-resolution cryo-electron microscopy structures and biochemical analyses reveal that PieF binds with nanomolar affinity to the NOT7 and NOT8 catalytic subunits of CCR4-NOT, obstructing RNA access and displacing a catalytic Mg²⁺ ion from the active site. Additionally, PieF prevents NOT7/8 from associating with their partner deadenylases NOT6/6L, inhibiting the assembly of a functional deadenylase complex. Consequently, PieF robustly blocks mRNA poly(A) tail shortening and degradation with striking potency and selectivity for NOT7/8. This inhibition of deadenylation by PieF impedes cell cycle progression in human cells, revealing a novel bacterial strategy to modulate host gene expression. |
External links | Nat Commun / PubMed:40651939 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.8 - 3.5 Å |
| Structure data | EMDB-47689, PDB-9e7t: EMDB-47690, PDB-9e7u: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-HOH: |
| Source |
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Keywords | GENE REGULATION / PieF / mRNA decay / deadenylation / CCR4-NOT / host-pathogen interactions |
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homo sapiens (human)
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