The Human T-Lymphotropic Virus Type 1 Tax Protein Inhibits Nonsense-Mediated mRNA Decay by Interacting with INT6/EIF3E and UPF1
| Autor: | Jürgen Wittmann, Madeleine Duc Dodon, Hervé Le Hir, Julia Neusiedler, Pierre Jalinot, Francesca Rende, Vincenzo Ciminale, Vincent Mocquet, Jean Philippe Robin, Jean-Michel Terme, Christelle Morris, David Cluet |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Viral protein
Protein subunit Eukaryotic Initiation Factor-3 RNA Stability T-Lymphocytes Immunology Nonsense-mediated decay Retroviridae Proteins Biology medicine.disease_cause Microbiology Jurkat cells Jurkat Cells Viral Proteins Virology Gene expression Transcriptional regulation medicine Humans RNA Messenger human T-cell leukaemia virus type 1 (HTLV-1) Messenger RNA Human T-lymphotropic virus 1 HEK 293 cells Gene Products tax Molecular biology Genome Replication and Regulation of Viral Gene Expression Basic-Leucine Zipper Transcription Factors HEK293 Cells Insect Science Trans-Activators RNA Helicases |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | et al. In this report, we analyzed whether the degradation of mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was affected in human T-lymphotropic virus type 1 (HTLV-1)-infected cells. This pathway was indeed strongly inhibited in C91PL, HUT102, and MT2 cells, and such an effect was also observed by the sole expression of the Tax protein in Jurkat and HeLa cells. In line with this activity, Tax binds INT6/EIF3E (here called INT6), which is a subunit of the translation initiation factor eukaryotic initiation factor 3 (eIF3) required for efficient NMD, as well as the NMD core factor upstream frameshift protein 1 (UPF1). It was also observed that Tax expression alters the morphology of processing bodies (P-bodies), the cytoplasmic structures which concentrate RNA degradation factors. The presence of UPF1 in these subcellular compartments was increased by Tax, whereas that of INT6 was decreased. In line with these effects, the level of the phosphorylated form of UPF1 was increased in the presence of Tax. Analysis of several mutants of the viral protein showed that the interaction with INT6 is necessary forNMD inhibition. The alteration ofmRNAstability was observed to affect viral transcripts, such as that coding for the HTLV-1 basic leucine zipper factor (HBZ), and also several cellular mRNAs sensitive to theNMDpathway. Our data indicate that the effect of Tax on viral and cellular gene expression is not restricted to transcriptional control but can also involve posttranscriptional regulation. © 2012, American Society for Microbiology. This work was supported by a fellowship (V.M.) and a grant from the Association pour la Recherche sur le Cancer and by a fellowship (J.N.) from the Ligue Nationale contre le Cancer. |
| Databáze: | OpenAIRE |
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