Proteomics

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Interactome of Eif4a2 in mouse embryonic stem cells

ABSTRACT: Cell fate transitions depend on balanced rewiring of transcription and translation programmes to enable ordered developmental progression. We identified a feedback loop between nonsense-mediated mRNA decay (NMD) and translation initiation, in which NMD controls the translation initiation factor Eif4a2 and its premature termination codon encoding isoform (Eif4a2-PTC). This leads to translation of a specific truncated protein, which elicits increased translation rates and is causative for significant delays in mouse embryonic stem cell differentiation. Using immunoprecipitation coupled with mass spectrometry, we identified the interactome of full length Eif4a2 (Eif4a2-iso1) and Eif4a2-PTC. We find that Eif4a2-iso1 is mainly involved in translation initiation, while unstable Eif4a2-PTC shows little interaction with translation initiation factors. Both isoforms can bind to mRNA, as indicated by the interaction with mRNA binding protein, such as NMD factors and Ago2. Finally, Eif4a2-iso1 and Eif4a2-PTC interact with key pluripotency factors, providing a potential explanation for how Eif4a2 controls ESC differentiation.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Markus Hartl  

LAB HEAD: Martin Leeb

PROVIDER: PXD019588 | Pride | 2022-03-09

REPOSITORIES: Pride

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20200204_QExHFX1_RSLC1_Galimberti_Leeb_MFPL_Eif4a2_rep1_E_70p.raw Raw
20200204_QExHFX1_RSLC1_Galimberti_Leeb_MFPL_Eif4a2_rep1_ISO1_70p.raw Raw
20200204_QExHFX1_RSLC1_Galimberti_Leeb_MFPL_Eif4a2_rep1_PTC_70p.raw Raw
20200204_QExHFX1_RSLC1_Galimberti_Leeb_MFPL_Eif4a2_rep1_WT_70p.raw Raw
20200204_QExHFX1_RSLC1_Galimberti_Leeb_MFPL_Eif4a2_rep2_E_70p.raw Raw
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Publications

Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expression levels of the translation initiation factor <i>Eif4a2</i> and its premature termination codon-encoding isoform (<i>Eif4a2</i><sup><i>PTC</i></sup  ...[more]

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