Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32074
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
Links: http://nar.oxfordjournals.org/content/42/5/3298
http://hdl.handle.net/2381/32074
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) (http://creativecommons.org/licenses/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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