转录起始过程通用转录因子TFIIH结构生物学研究

基因转录是生命体最基础的生命活动。基因转录是指遗传信息（DNA）经过多蛋白复合物的参与指导RNA合成的过程。这个过程涉及多个蛋白复合物包括RNA聚合酶II、通用转录因子、基因特异的转录因子、中介体复合物等。其中通用转录因子TFIIH具有解旋酶和ATPase活性，可以催化转录起始过程“转录起始泡”的形成。对于转录起始过程至关重要。真核生物TFIIH包含核心复合物模块、TFIIK模块，共11个亚基。TFIIH核心复合物由Tfb1、Tfb2、Tfb4、Tfb5、Rad3、Ssl1等亚基组成，TFIIK及Ssl2会组装到这个核心复合物上形成完整的TFIIH。本研究拟对TFIIH开展高分辨率结构生物学研究，希望通过解析其高分辨率结构以及其与中介体复合物和RNA聚合酶II的相互作用模式，深化转录起始过程的认识。

Pre-initiation complex (PIC) has fundamental roles in transcriptional regulation in all eukaryotes. PIC comprises of RNA polymerase II, general transcription factors, Mediator complex and gene-specific transcription factors. The general transcription factors, including TFIIA, TFIIB, TFIID, TFIIF, TFIIH and TFIIS, are conserved among all eukaryote organisms. TFIIH possess helicase and ATPase activity that can promote the formation of transcription bubbles. TFIIH consists of 11 subunits, which have been divided into two modules, the core sub-complex and TFIIK module. Among these subunits, Tfb1, Tfb2, Tfb4, Tfb5, Rad3 and Ssl1 assemble as a stable core complex, which recruits Ssl2 and TFIIK to form an intact TFIIH complex. TFIIH is the only one general transcription factor that has no high-resolution structure yet. Our this proposal aims at the structural determination of TFIIH and its interaction with other protein complexes such as RNA polymerase II and Mediator complex and elucidating the mechanism of the transcriptional regulation in all eukaryotes.