Wang H Y, Xu X, Ding J H, Bermingham J R, Fu X D
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Mol Cell. 2001 Feb;7(2):331-42. doi: 10.1016/s1097-2765(01)00181-2.
Molecular diversity via alternative splicing is important for cellular function and development. SR proteins are strong candidate regulators of alternative splicing because they can modulate splice site selection. However, endogenous substrates for SR proteins are largely unknown, and their roles as splicing regulators in vertebrate development are unclear. Here we report that Cre-mediated conditional deletion of the prototypical SR protein SC35 in the thymus causes a defect in T cell maturation. Deletion of SC35 alters alternative splicing of CD45, a receptor tyrosine phosphatase known to be regulated by differential splicing during thymocyte development and activation. This study establishes a model to address the function of SR proteins in physiological settings and reveals a critical role of SC35 in a T cell-specific regulated splicing pathway.
通过可变剪接产生的分子多样性对于细胞功能和发育至关重要。SR蛋白是可变剪接的有力候选调节因子，因为它们可以调节剪接位点的选择。然而，SR蛋白的内源性底物在很大程度上尚不清楚，并且它们在脊椎动物发育中作为剪接调节因子的作用也不明确。在此我们报告，Cre介导的胸腺中典型SR蛋白SC35的条件性缺失导致T细胞成熟缺陷。SC35的缺失改变了CD45的可变剪接，CD45是一种受体酪氨酸磷酸酶，已知在胸腺细胞发育和激活过程中受差异剪接调控。本研究建立了一个模型来探讨SR蛋白在生理环境中的功能，并揭示了SC35在T细胞特异性调节剪接途径中的关键作用。
