Rodríguez-Navarro Susana, Fischer Tamás, Luo Ming-Juan, Antúnez Oreto, Brettschneider Susanne, Lechner Johannes, Pérez-Ortín Jose E, Reed Robin, Hurt Ed
Biochemie-Zentrum der Universität Heidelberg (BZH), Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
Cell. 2004 Jan 9;116(1):75-86. doi: 10.1016/s0092-8674(03)01025-0.
Gene expression is a coordinated multistep process that begins with transcription and RNA processing in the nucleus followed by mRNA export to the cytoplasm for translation. Here we report the identification of a protein, Sus1, which functions in both transcription and mRNA export. Sus1 is a nuclear protein with a concentration at the nuclear pores. Biochemical analyses show that Sus1 interacts with SAGA, a large intranuclear histone acetylase complex involved in transcription initiation, and with the Sac3-Thp1 complex, which functions in mRNA export with specific nuclear pore proteins at the nuclear basket. DNA macroarray analysis revealed that Sus1 is required for transcription regulation. Moreover, chromatin immunoprecipitation showed that Sus1 is associated with the promoter of a SAGA-dependent gene during transcription activation. Finally, mRNA export is impaired in sus1 mutants. These data provide an unexpected connection between the SAGA histone acetylase complex and the mRNA export machinery.
基因表达是一个协调的多步骤过程,始于细胞核内的转录和RNA加工,随后mRNA输出到细胞质进行翻译。在此,我们报告一种蛋白质Sus1的鉴定,它在转录和mRNA输出过程中均发挥作用。Sus1是一种核蛋白,集中分布于核孔。生化分析表明,Sus1与SAGA(一种参与转录起始的大型核内组蛋白乙酰化酶复合物)以及Sac3-Thp1复合物相互作用,Sac3-Thp1复合物与特定核孔蛋白在核篮处协同发挥mRNA输出功能。DNA微阵列分析显示,Sus1是转录调控所必需的。此外,染色质免疫沉淀表明,在转录激活过程中,Sus1与一个依赖SAGA的基因的启动子相关联。最后,sus1突变体中的mRNA输出受损。这些数据揭示了SAGA组蛋白乙酰化酶复合物与mRNA输出机制之间意想不到的联系。