Abstract
The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements of the 3′-end core cleavage complex involved in cleavage and polyadenylation (CPA), including CPSF3, the enzyme responsible for cleavage, as well as its co-factors CPSF1, CPSF2, CPSF4, Symplekin, WDR33, and FIP1L1. Using multiple strategies, we demonstrate that eIF4E stimulates 3′-end cleavage of selected RNAs. eIF4E physically interacts with CPSF3, CPSF1, and uncleaved target RNA, suggesting it acts directly and indirectly on the pathway. Through these effects, eIF4E can generate better substrates for its mRNA export and translation activities. Thus, we identified an unanticipated function for eIF4E in 3′-end processing of specific target RNAs, and this function could potentially affect the expression of a broad range of oncoproteins. Davis et al. demonstrate that the eukaryotic translation initiation factor eIF4E, which is usually associated with nuclear export and translation of specific transcripts, also acts in 3′-end processing of selected RNAs. Through these effects, eIF4E can generate better substrates for its export and translation activities and, thus, modulate the proteome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1397-1408.e4 |
| Journal | Cell reports |
| Volume | 27 |
| Issue number | 5 |
| DOIs | |
| State | Published - Apr 30 2019 |
Funding
Many thanks for the technical assistance of Drs. Biljana Culjkovic-Kraljacic, Luce Skrabanek, Laurent Volpon, and Heloise Chasse. Research reported in this publication was supported by the National Cancer Institute of the NIH under grants R01CA080728 and RO1CA098571 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also supported by Canadian Institutes of Health Research PJT159785 . K.L.B.B. holds a Canada Research Chair and M.R.D. holds a Cole Foundation Postdoctoral Fellowship and an Institute for Research in Immunology and Cancer Postdoctoral Fellowship Award. Figure 1 A derivative of Figure 2 in Neve et al. (2017) , used under CC BY NC 4 ( https://creativecommons.org/licenses/by-nc/4.0/ ) and is licensed under CC BY NC 4 by M.R.D., M.D., and K.L.B.B. Many thanks for the technical assistance of Drs. Biljana Culjkovic-Kraljacic, Luce Skrabanek, Laurent Volpon, and Heloise Chasse. Research reported in this publication was supported by the National Cancer Institute of the NIH under grants R01CA080728 and RO1CA098571. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also supported by Canadian Institutes of Health Research PJT159785. K.L.B.B. holds a Canada Research Chair and M.R.D. holds a Cole Foundation Postdoctoral Fellowship and an Institute for Research in Immunology and Cancer Postdoctoral Fellowship Award. Figure 1A derivative of Figure 2 in Neve et al. (2017), used under CC BY NC 4 (https://creativecommons.org/licenses/by-nc/4.0/) and is licensed under CC BY NC 4 by M.R.D. M.D. and K.L.B.B. M.R.D. designed and performed experiments, analyzed data, and wrote the manuscript; M.D. designed and performed experiments and analyzed data; and K.L.B.B. analyzed data, designed experiments, and wrote the manuscript. The authors have no competing interests.
Keywords
- nuclear RNA export
- polyadenylation
- translation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology