Translocation of a Cell Surface Spliceosomal Complex Induces Alternative Splicing Events and Lymphoma Cell Necrosis.,Cell Chemical Biology

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Translocation of a Cell Surface Spliceosomal Complex Induces Alternative Splicing Events and Lymphoma Cell Necrosis.
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2019-03-28 , DOI: 10.1016/j.chembiol.2019.02.016
Sonal S Tonapi ₁ , Vaishali Pannu ₁ , Janet E Duncan ₁ , Matthew Rosenow ₁ , Anthony Helmstetter ₁ , Daniel Magee ₁ , Qing Zhang ₁ , Teresa T Tinder ₁ , Melissa Richards ₁ , David D Halbert ₁ , Michael Famulok ₂ , David Spetzler ₁ , Mark R Miglarese ₁ , Heather A O'Neill ₁ , Günter Mayer ₂

Affiliation

Spliceosomal dysregulation dramatically affects many cellular processes, notably signal transduction, metabolism, and proliferation, and has led to the concept of targeting intracellular spliceosomal proteins to combat cancer. Here we show that a subset of lymphoma cells displays a spliceosomal complex on their surface, which we term surface spliceosomal complex (SSC). The SSC consists of at least 13 core components and was discovered as the binding target of the non-Hodgkin's lymphoma-specific aptamer C10.36. The aptamer triggers SSC internalization, causing global changes in alternative splicing patterns that eventually lead to necrotic cell death. Our study reveals an exceptional spatial arrangement of a spliceosomal complex and defines it not only as a potential target of anti-cancer drugs, but also suggests that its localization plays a fundamental role in cell survival.

中文翻译：

细胞表面剪接体复合物的易位引起替代剪接事件和淋巴瘤细胞坏死。

剪接体失调显着影响许多细胞过程，特别是信号转导，代谢和增殖，并导致了靶向细胞内剪接体蛋白以对抗癌症的概念。在这里，我们显示了淋巴瘤细胞的一个子集在其表面上显示出一个剪接体复合体，我们称其为表面剪接体复合体（SSC）。SSC至少包含13个核心成分，并被发现是非霍奇金淋巴瘤特异性适体C10.36的结合靶标。适体触发SSC内在化，导致替代剪接模式的整体变化，最终导致坏死细胞死亡。我们的研究揭示了剪接体复合物的特殊空间排列方式，并将其不仅定义为抗癌药物的潜在靶点，

更新日期：2019-05-16

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