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Differential splicing generates Tvl-1/RFXANK isoforms with different functions.

Santasabuj Das·Jun-Hsiang Lin·Joseph Papamatheakis·Yuri Sykulev·Philip N Tsichlis
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Abstract

Earlier studies have shown that Tvl-1 gives rise to at least two differentially spliced mRNAs, one of which (Tvl-S) encodes a protein that lacks amino acids 91-112. DNA binding of RFX complexes assembled in the presence of Tvl-S is impaired. As a result, Tvl-S does not support the expression of Class II major histocompatibility complex (MHC) genes. Here, we show that the reason Tvl-S is inactive as a transcriptional regulator of Class II MHC genes is that the RFX complexes assembled in the presence of Tvl-S are unstable. Additionally, we show that interferon-gamma, which induces Class II MHC gene expression in 293 cells, promotes a shift in the splicing pattern of RFXANK/Tvl-1 toward the transcriptionally active Tvl-L isoform, suggesting that differential splicing of Tvl-1 is a signal-regulated process. Finally, we show that Tvl-1 regulates the expression of non-MHC genes. One such gene encodes the ephrin receptor EphA3. Since both Tvl-L and Tvl-S are identical in their ability to induce the expression of EphA3, we conclude that Tvl-1 regulates the expression of non-MHC genes by RFX-independent mechanisms.

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Adaptor Proteins, Signal TransducingAlternative SplicingAmino Acid SequenceAnkyrin RepeatBase SequenceCarrier ProteinsDNA-Binding ProteinsGene Expression RegulationGenes, MHC Class IIHumansInterferon-gammaMacromolecular SubstancesMicroscopy, FluorescenceMolecular Sequence DataOligonucleotide Array Sequence AnalysisOligonucleotidesProtein BindingProtein IsoformsReceptor, EphA3Regulatory Factor X Transcription FactorsTranscription FactorsTranscription, GeneticTumor Cells, CulturedJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Santasabuj Das, Jun-Hsiang Lin, Joseph Papamatheakis, Yuri Sykulev, Philip N Tsichlis. 2002-09-04. Differential splicing generates Tvl-1/RFXANK isoforms with different functions.. https://doi.org/10.1074/jbc.m204117200

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