CELF1 is an EIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs

Chaudhury, A.; Pal, R.; Kongchan, N.; Zhao, N.; Zhu, Y.; Olokpa, E.; Cheema, S.; del Rincon, S.; Reineke, L. C.; Mao, S.; Llyod, R. E.; Sardiello, M.; Rosen, J. M.; Neilson, J. R.

doi:10.1101/640300

bioRxiv · 10.1101/640300

CELF1 is an EIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs

Chaudhury, A.·Pal, R.·Kongchan, N.·Zhao, N.·Zhu, Y.·Olokpa, E.·Cheema, S.·del Rincon, S.·Reineke, L. C.·Mao, S.·Llyod, R. E.·Sardiello, M.·Rosen, J. M.·Neilson, J. R.

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Abstract

Mounting evidence is revealing a granularity within gene regulation that occurs at the level of mRNA translation. Within mammalian cells, canonical cap-dependent mRNA translation is dependent upon the interaction between the m7G cap-binding protein eukaryotic initiation factor 4E (eIF4E) and the scaffolding protein eukaryotic initiation factor 4G (eIF4G), the latter of which facilitates pre-translation initiation complex assembly, mRNA circularization, and ultimately ribosomal scanning. In breast epithelial cells, we previously demonstrated that the CELF1 RNA-binding protein promotes the translation of epithelial to mesenchymal transition (EMT) effector mRNAs containing GU-rich elements (GREs) within their 3 untranslated regions (UTRs). Here we show that within this context, CELF1 directly binds to both the eIF4E cap-binding protein and Poly(A) binding protein (PABP), promoting translation of GRE-containing mRNAs in mesenchymal cells. Disruption of this CELF1/eIF4E interaction inhibits both EMT induction and experimental metastasis. Our findings illustrate a novel way in which non-canonical mechanisms of translation initiation underlie transitional cellular states within the context of development or human disease.

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Chaudhury, A., Pal, R., Kongchan, N., Zhao, N., Zhu, Y., Olokpa, E., Cheema, S., del Rincon, S., Reineke, L. C., Mao, S., Llyod, R. E., Sardiello, M., Rosen, J. M., Neilson, J. R.. 2019-05-16. CELF1 is an EIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs. https://doi.org/10.1101/640300

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