A structural insight into the C-terminal RNA recognition motifs of T-cell intracellular antigen-1 protein

7 Páginas, 5 figurasT-cell intracellular antigen-1 (TIA-1) plays a pleiotropic role in cell homeostasis through the regulation of alternative pre-mRNA splicing and mRNA translation by recognising uridine-rich sequences of RNAs. TIA-1 contains three RNA recognition motifs (RRMs) and a glutamine-rich domain. Here, we characterise its C-terminal RRM2 and RRM3 domains. Notably, RRM3 contains an extra novel N-terminal α-helix (α1) which protects its single tryptophan from the solvent exposure, even in the two-domain RRM23 context. The α1 hardly affects the thermal stability of RRM3. On the contrary, RRM2 destabilises RRM3, indicating that both modules are tumbling together, which may influence the RNA binding activity of TIA-1.The authors wish to thank the Andalusian Government (P07-CVI-02896 and BIO198) for financial support. The plasmid containing the TIA-1 full-length protein was kindly provided by Dr. M. Gorospe (National Institutes of Health, Baltimore, USA) and Dr. P. Anderson (Harvard Medical School, Boston, USA). We are grateful to Prof. Miguel A. De la Rosa for critical reading of the manuscript.Peer reviewe