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  • Meeting abstract
  • Open Access

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

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  • 1Email author
Retrovirology20118 (Suppl 1) :A139

  • Published:


  • Posttranscriptional Level
  • Premature Stop Codon
  • mRNA Degradation
  • Major Actor
  • mRNA Decay

The Nonsense Mediated mRNA Decay (NMD) regulates the expression of many genes such as GADD45a and lead to the degradation of mRNA exhibiting a premature 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 associated 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 network 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 immunoprecipitations 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.

Authors’ Affiliations

Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, 69364, cedex 07, France
Department of Oncology and Surgical Sciences and Istituto Oncologico Veneto-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger- Center, University of Erlangen-Nürnberg, Erlangen, D-91054, Germany
Virologie 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


© Mocquet et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.