Kumar Amit O, Swenson Matthew C, Benning Matthew M, Kielkopf Clara L
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Biochem Biophys Res Commun. 2008 Mar 21;367(4):813-9. doi: 10.1016/j.bbrc.2008.01.027. Epub 2008 Jan 15.
T-cell-restricted intracellular antigen-1 (TIA-1) regulates alternative pre-mRNA splicing in the nucleus, and mRNA translation in the cytoplasm, by recognizing uridine-rich sequences of RNAs. As a step towards understanding RNA recognition by this regulatory factor, the X-ray structure of the central RNA recognition motif (RRM2) of human TIA-1 is presented at 1.95A resolution. Comparison with structurally homologous RRM-RNA complexes identifies residues at the RNA interfaces that are conserved in TIA-1-RRM2. The versatile capability of RNP motifs to interact with either proteins or RNA is reinforced by symmetry-related protein-protein interactions mediated by the RNP motifs of TIA-1-RRM2. Importantly, the TIA-1-RRM2 structure reveals the locations of mutations responsible for inhibiting nuclear import. In contrast with previous assumptions, the mutated residues are buried within the hydrophobic interior of the domain, where they would be likely to destabilize the RRM fold rather than directly inhibit RNA binding.
T细胞限制性细胞内抗原-1（TIA-1）通过识别富含尿苷的RNA序列，在细胞核中调节前体mRNA的可变剪接，并在细胞质中调节mRNA翻译。作为理解这种调节因子对RNA识别的一个步骤，人类TIA-1的中央RNA识别基序（RRM2）的X射线结构以1.95埃的分辨率呈现。与结构同源的RRM-RNA复合物进行比较，确定了TIA-1-RRM2中RNA界面上保守的残基。TIA-1-RRM2的RNP基序介导的对称相关蛋白质-蛋白质相互作用增强了RNP基序与蛋白质或RNA相互作用的多功能能力。重要的是，TIA-1-RRM2结构揭示了负责抑制核输入的突变位置。与先前的假设相反，突变残基埋藏在结构域的疏水内部，在那里它们可能会破坏RRM折叠的稳定性，而不是直接抑制RNA结合。
