Distinct recruitment of human eIF4E isoforms to processing bodies and stress granules.

BMC Mol Biol

Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Viničná 5, 128 00, Prague 2, Czech Republic.

Published: August 2016

AI Article Synopsis

  • The study investigates the localization of different eIF4E protein isoforms, specifically eIF4E2 and eIF4E3, which have received less attention compared to the well-studied eIF4E1.
  • eIF4E3_A was found to localize to stress granules during stress conditions like heat shock and arsenite exposure but does not localize to processing bodies, while eIF4E3_B does not localize to stress granules at all.
  • The findings suggest that different eIF4E isoforms and their variants play unique roles in cellular stress responses by showing distinct patterns of localization and interactions with other translation initiation factors.

Article Abstract

Background: Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs). In this study, we focused on the subcellular localization of a representative compendium of eIF4E protein isoforms, particularly on the less studied members of the human eIF4E protein family, eIF4E2 and eIF4E3.

Results: We showed that unlike eIF4E1, its less studied isoform eIF4E3_A, encoded by human chromosome 3, localized to stress granules but not PBs upon both heat shock and arsenite stress. Furthermore, we found that eIF4E3_A interacts with human translation initiation factors eIF4G1, eIF4G3 and PABP1 in vivo and sediments into the same fractions as canonical eIF4E1 during polysome analysis in sucrose gradients. Contrary to this finding, the truncated human eIF4E3 isoform, eIF4E3_B, showed no localization to SGs and no binding to eIF4G. We also highlighted that eIF4E2 may exhibit distinct functions under different stresses as it readily localizes to P-bodies during arsenite and heat stresses, whereas it is redirected to stress granules only upon heat shock. We extended our study to a number of protein variants, arising from alternative mRNA splicing, of each of the three eIF4E isoforms. Our results surprisingly uncovered differences in the ability of eIF4E1_1 and eIF4E1_3 to form stress granules in response to cellular stresses.

Conclusion: Our comparison of all three human eIF4E isoforms and their protein variants enriches the intriguing spectrum of roles attributed to the eukaryotic initiation translation factors of the 4E family, which exhibit a distinctive localization within different RNA granules under different stresses. The localization of eIF4E3_A to stress granules, but not to processing bodies, along with its binding to eIF4G and PABP1 suggests a role of human eIF4E3_A in translation initiation rather than its involvement in a translational repression and mRNA decay and turnover. The localization of eIF4E2 to stress granules under heat shock but not arsenite stress indicates its distinct function in cellular response to these stresses and points to the variable protein content of SGs as a consequence of different stress insults.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006505PMC
http://dx.doi.org/10.1186/s12867-016-0072-xDOI Listing

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