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Title: Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated silencing.
Authors: Kamenska, A.
Lu, Wei-Ting
Kubacka, D.
Broomhead, H.
Minshall, N.
Bushell, Martin
Standart, N.
First Published: 13-Dec-2013
Publisher: Oxford University Press (OUP)
Citation: Nucleic Acids Research, 2014, 42 (5), pp. 3298-3313
Abstract: A key player in translation initiation is eIF4E, the mRNA 5' cap-binding protein. 4E-Transporter (4E-T) is a recently characterized eIF4E-binding protein, which regulates specific mRNAs in several developmental model systems. Here, we first investigated the role of its enrichment in P-bodies and eIF4E-binding in translational regulation in mammalian cells. Identification of the conserved C-terminal sequences that target 4E-T to P-bodies was enabled by comparison of vertebrate proteins with homologues in Drosophila (Cup and CG32016) and Caenorhabditis elegans by sequence and cellular distribution. In tether function assays, 4E-T represses bound mRNA translation, in a manner independent of these localization sequences, or of endogenous P-bodies. Quantitative polymerase chain reaction and northern blot analysis verified that bound mRNA remained intact and polyadenylated. Ectopic 4E-T reduces translation globally in a manner dependent on eIF4E binding its consensus Y30X4L site. In contrast, tethered 4E-T continued to repress translation when eIF4E-binding was prevented by mutagenesis of YX4L, and modestly enhanced the decay of bound mRNA, compared with wild-type 4E-T, mediated by increased binding of CNOT1/7 deadenylase subunits. As depleting 4E-T from HeLa cells increased steady-state translation, in part due to relief of microRNA-mediated silencing, this work demonstrates the conserved yet unconventional mechanism of 4E-T silencing of particular subsets of mRNAs.
DOI Link: 10.1093/nar/gkt1265
ISSN: 0305-1048
eISSN: 1362-4962
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0) (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Description: PMCID: PMC3950672 Supplementary Data are available at NAR Online, including [44].
Appears in Collections:Reports, Dept. of Biochemistry

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