Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Oncogene. 2010 Mar 25;29(12):1821-34. doi: 10.1038/onc.2009.473. Epub 2010 Jan 18.
The nucleolus is one of the functional nuclear compartments in which the ribosome biogenesis takes place. Proteomic analysis revealed a large number of nucleolar proteins that are involved in diverse cellular processes, including biogenesis of ribonucleoprotein particles, stress responses, cell proliferation and cell cycle progression. Here, we report that in response to transcription repression-induced nucleolar segregation, B23, a nucleolar protein required for rRNA processing, is localized to the cytoplasm and forms a complex with the mRNA-binding proteins hnRNPU and hnRNPA1 in a sequential manner. In addition, RNA Polymerase I, but not RNA Polymerase II inhibition, was found to account for the translocation-dependent assembly of B23/hnRNPU/hnRNPA1. We also showed that interactions among these proteins are regulated by hnRNPU-bound mRNAs such as the 3'-untranslated region (UTR) of Bcl-xL mRNA. Ectopically expressed 3'-UTR of Bcl-xL mRNA, which disrupted the interactions among B23, hnRNPU and hnRNPA1, led to enhanced cell apoptosis induced by either actinomycin D treatment or mitotic arrest. Overall, these data highlight a novel function of B23 as a stress sensor in the assembly of B23/hnRNPU/hnRNPA1 complex to promote cell survival.
核仁是核糖体生物发生的功能核区室之一。蛋白质组学分析揭示了大量参与多种细胞过程的核仁蛋白，包括核糖核蛋白颗粒的生物发生、应激反应、细胞增殖和细胞周期进程。在这里，我们报告说，在转录抑制诱导的核仁分离反应中，B23 是一种核仁蛋白，对于 rRNA 加工是必需的，它定位于细胞质中，并以顺序方式与 mRNA 结合蛋白 hnRNPU 和 hnRNPA1 形成复合物。此外，发现 RNA 聚合酶 I（而不是 RNA 聚合酶 II 抑制）导致依赖于易位的 B23/hnRNPU/hnRNPA1 组装。我们还表明，这些蛋白质之间的相互作用受 hnRNPU 结合的 mRNA 调节，例如 Bcl-xL mRNA 的 3'-非翻译区（UTR）。异位表达 Bcl-xL mRNA 的 3'-UTR，破坏了 B23、hnRNPU 和 hnRNPA1 之间的相互作用，导致放线菌素 D 处理或有丝分裂阻滞诱导的细胞凋亡增强。总体而言，这些数据突出了 B23 作为 B23/hnRNPU/hnRNPA1 复合物组装中的应激传感器的新功能，以促进细胞存活。
