Artículo
TIA-1 RRM23 binding and recognition of target oligonucleotides
Autor/es | Waris, Saboora
García Mauriño, Sofía M. Sivakumaran, Andrew Díaz Moreno, Irene |
Departamento | Universidad de Sevilla. Departamento de Biología Vegetal y Ecología |
Fecha de publicación | 2017 |
Fecha de depósito | 2017-06-01 |
Publicado en |
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Resumen | TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with ... TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with specificity for U-rich sequences directed by RRM2. It has recently been shown that RRM3 also contributes to binding, with preferential binding for C-rich sequences. Here we designed UC-rich and CU-rich 10-nt sequences for engagement of both RRM2 and RRM3 and demonstrated that the TIA-1 RRM23 construct preferentially binds the UC-rich RNA ligand (5΄-UUUUUACUCC-3΄). Interestingly, this binding depends on the presence of Lys274 that is C-terminal to RRM3 and binding to equivalent DNA sequences occurs with similar affinity. Small-angle X-ray scattering was used to demonstrate that, upon complex formation with target RNA or DNA, TIA-1 RRM23 adopts a compact structure, showing that both RRMs engage with the target 10-nt sequences to form the complex. We also report the crystal structure of TIA-1 RRM2 in complex with DNA to 2.3 Å resolution providing the first atomic resolution structure of any TIA protein RRM in complex with oligonucleotide. Together our data support a specific mode of TIA-1 RRM23 interaction with target oligonucleotides consistent with the role of TIA-1 in binding RNA to regulate gene expression |
Cita | Waris, S., García Mauriño, S.M., Sivakumaran, A. y Díaz Moreno, I. (2017). TIA-1 RRM23 binding and recognition of target oligonucleotides. Nucleic Acids Research, 45 (8), 49448-84957. |
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