Ciminale, Vincenzo

Duc Dodon, Madeleine

Jalinot, Pierre

Mocquet, Vincent

Morris, Christelle

Neusiedler, Julia

Rende, Francesca

Terme, Jean-Michel

Wittman, Jürgen

English

PubMed

Mocquet Vincent

Neusiedler Julia

Rende Francesca

Terme Jean-Michel

Morris Christelle

Wittman Jürgen

Duc Dodon Madeleine

Ciminale Vincenzo

Jalinot Pierre

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Retrovirology

The HTLV-1 Tax protein inhibits nonsense-mediated mRNA decay by interacting with INT6/EIF3E and UPF1

Vincent Mocquet

Julia Neusiedler

Francesca Rende

Jean-Michel Terme

Christelle Morris

Jürgen Wittman

Madeleine Duc Dodon

Vincenzo Ciminale

Pierre Jalinot

Crossref

Springer - Publisher Connector

MEETING ABSTRACT Open Access
The HTLV-1 Tax protein inhibits nonsense-
mediated mRNA decay by interacting with
INT6/EIF3E and UPF1
Vincent Mocquet1, Julia Neusiedler1, Francesca Rende2, Jean-Michel Terme1, Christelle Morris1, Jürgen Wittman3,
Madeleine Duc Dodon4, Vincenzo Ciminale2, Pierre Jalinot1*
From 15th International Conference on Human Retroviruses: HTLV and Related Viruses
Leuven and Gembloux, Belgium. 5-8 June 2011
The Nonsense Mediated mRNA Decay (NMD) regulates
the expression of many genes such as GADD45a and
lead to the degradation of mRNA exhibiting a prema-
ture STOP codon (PTC). The cellular protein INT6 has
been identified by our team as a major actor of this
pathway. We also demonstrated that INT6 interacts
with Tax, the transcriptional activator of HTLV-1 that
plays a major role in the cellular transformation asso-
ciated to HTLV. As a consequence, a blockade of the
NMD pathway by Tax through INT6 binding could
alter the genetic expression profil of an infected cell and
play a role in the emergence of a transformed clone.
We first showed that Tax increases the half-life of
PTC containing reporter genes as well as endogenous
targets of the NMD such as gadd45a. Then we
decrypted by immunoprecipitation experiments, a net-
work of interactions between the viral protein, INT6
and the UPFs. These results, combined with confocal
microscopy observations, suggest that Tax (1) sequesters
INT6 out of reach from UPF1/2 and (2) interacts with
phospho-UPF1, inhibiting its dephosphorylation which
is indispensable during NMD. Interestingly, Tax causes
a strong increase in the size and number of P.bodies,
where UPF1 accumulates. Finally, RNA immunoprecipi-
tations demonstrated that Tax is associated with the
mRNA targeted by the NMD pathway.
Collectively these data show that in addition to its role
in transcriptional activation, Tax can also interfere at
the posttranscriptional level with the regulation of
mRNA degradation through the NMD pathway.
Author details
1Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, Ecole Normale
Supérieure de Lyon, Lyon, 69364, cedex 07, France. 2Department of
Oncology and Surgical Sciences and Istituto Oncologico Veneto-Istituto di
Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy. 3Division of
Molecular Immunology, Department of Internal Medicine III, Nikolaus-
Fiebiger- Center, University of Erlangen-Nürnberg, Erlangen, D-91054,
Germany. 4Virologie Humaine, Unité 758, Institut National de la Santé et de
la Recherche Médicale, Ecole Normale Supérieure de Lyon, Institut Fédératif
de Recherche 128 Biosciences Lyon Gerland, Lyon, cedex 07, France.
Published: 6 June 2011
doi:10.1186/1742-4690-8-S1-A139
Cite this article as: Mocquet et al.: The HTLV-1 Tax protein inhibits
nonsense-mediated mRNA decay by interacting with INT6/EIF3E and
UPF1. Retrovirology 2011 8(Suppl 1):A139.
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* Correspondence: pjalinot@ens-lyon.fr
1Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, Ecole Normale
Supérieure de Lyon, Lyon, 69364, cedex 07, France
Full list of author information is available at the end of the article
Mocquet et al. Retrovirology 2011, 8(Suppl 1):A139
http://www.retrovirology.com/content/8/S1/A139
© 2011 Mocquet et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


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The HTLV-1 Tax protein inhibits nonsense-mediated mRNA decay by interacting with INT6/EIF3E and UPF1

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