Abstract B08: eIF4E3 forms a novel cap-binding complex for mRNA translation initiation

• Published in: Clinical cancer research 2015-09, Vol.21 (17_Supplement), p.B08-B08
• Main Authors: Landon, Ari L., Muniandy, Parameswary A, Houng, Simone, Shetty, Amol, Becker, Kevin, Borden, Katherine, Gartenhaus, Ronald B.
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1557-3265.HEMMAL14-B08

Dysregulation of mRNA translation can alter the cellular phenotype leading to cancer initiation, maintenance, progression, invasion or metastasis. Cap-dependent translation is the primary mechanism of mRNA translation in eukaryotic cells. The conventional cap-binding complex, eIF4F consists of three components including eIF4A, eIF4G and eIF4E1. eIF4E1 binds the 7-methyl-guanosine-cap (cap) structure in the mRNA and functions to bridge mRNA to the ribosome. eIF4E3 is another member of the eIF4E family that has been recently shown to bind cap using biophysical approach. We explored the biological function of eIF4E3 in a diffuse large B-cell lymphoma model. We found that in the absence or lack of eIF4E1 phosphorylation, eIF4E3 expression is enhanced, and this increases the cap-binding ability of eIF4E3. We find that eIF4E3 also physically associates with the components of the cap-binding complex eIF4A and eIF4G, essentially forming a novel cap-binding complex. We interrogated the functional capacity of the eIF4E3-mediated translation by analyzing the translatome and transcriptome of eIF4E3 expressing cells. eIF4E3 and eIF4E1 mutually regulate a high fraction of total mRNA transcripts, while exclusively modulating translation of select messages. Interestingly, we identified selective motif enrichments in the 5'UTR that may facilitate transcript selection by eIF4E1 or eIF4E3. Together, we have identified a novel cap-binding complex consisting of eIF4A, eIF4G and eIF4E3, which can initiate mRNA translation of select messages. Citation Format: Ari L. Landon, Parameswary A Muniandy, Simone Houng, Amol Shetty, Kevin Becker, Katherine Borden, Ronald B. Gartenhaus. eIF4E3 forms a novel cap-binding complex for mRNA translation initiation. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B08.