eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR

The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In the cytoplasm, recognition of the 5′ m7G cap moiety on all mRNAs is sufficient for their functional interaction with eIF4E. In contrast, we have shown that in...

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Main Authors:	Culjkovic, Biljana, Topisirovic, Ivan, Skrabanek, Lucy, Ruiz-Gutierrez, Melisa, Borden, Katherine L.B.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171863/

id	pubmed-2171863
recordtype	oai_dc
spelling	pubmed-21718632008-03-05 eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR Culjkovic, Biljana Topisirovic, Ivan Skrabanek, Lucy Ruiz-Gutierrez, Melisa Borden, Katherine L.B. Research Articles The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In the cytoplasm, recognition of the 5′ m7G cap moiety on all mRNAs is sufficient for their functional interaction with eIF4E. In contrast, we have shown that in the nucleus eIF4E associates and promotes the nuclear export of cyclin D1, but not GAPDH or actin mRNAs. We determined that the basis of this discriminatory interaction is an ∼100-nt sequence in the 3′ untranslated region (UTR) of cyclin D1 mRNA, we refer to as an eIF4E sensitivity element (4E-SE). We found that cyclin D1 mRNA is enriched at eIF4E nuclear bodies, suggesting these are functional sites for organization of specific ribonucleoproteins. The 4E-SE is required for eIF4E to efficiently transform cells, thereby linking recognition of this element to eIF4E mediated oncogenic transformation. Our studies demonstrate previously uncharacterized fundamental differences in eIF4E-mRNA recognition between the nuclear and cytoplasmic compartments and further a novel level of regulation of cellular proliferation. The Rockefeller University Press 2005-04-25 /pmc/articles/PMC2171863/ /pubmed/15837800 http://dx.doi.org/10.1083/jcb.200501019 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Culjkovic, Biljana Topisirovic, Ivan Skrabanek, Lucy Ruiz-Gutierrez, Melisa Borden, Katherine L.B.
spellingShingle	Culjkovic, Biljana Topisirovic, Ivan Skrabanek, Lucy Ruiz-Gutierrez, Melisa Borden, Katherine L.B. eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
author_facet	Culjkovic, Biljana Topisirovic, Ivan Skrabanek, Lucy Ruiz-Gutierrez, Melisa Borden, Katherine L.B.
author_sort	Culjkovic, Biljana
title	eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
title_short	eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
title_full	eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
title_fullStr	eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
title_full_unstemmed	eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
title_sort	eif4e promotes nuclear export of cyclin d1 mrnas via an element in the 3′utr
description	The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In the cytoplasm, recognition of the 5′ m7G cap moiety on all mRNAs is sufficient for their functional interaction with eIF4E. In contrast, we have shown that in the nucleus eIF4E associates and promotes the nuclear export of cyclin D1, but not GAPDH or actin mRNAs. We determined that the basis of this discriminatory interaction is an ∼100-nt sequence in the 3′ untranslated region (UTR) of cyclin D1 mRNA, we refer to as an eIF4E sensitivity element (4E-SE). We found that cyclin D1 mRNA is enriched at eIF4E nuclear bodies, suggesting these are functional sites for organization of specific ribonucleoproteins. The 4E-SE is required for eIF4E to efficiently transform cells, thereby linking recognition of this element to eIF4E mediated oncogenic transformation. Our studies demonstrate previously uncharacterized fundamental differences in eIF4E-mRNA recognition between the nuclear and cytoplasmic compartments and further a novel level of regulation of cellular proliferation.
publisher	The Rockefeller University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171863/
_version_	1611424735198969856

eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR

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