本文轉自BioArt
北京時間5月25日凌晨，Science在線發表了施一公課題組題為“Structures of the fully assembledSaccharomyces cerevisiaespliceosome before activation”的研究論文，解析了釀酒酵母平均分辨率分別為3.3-4.6 Å以及3.9 Å的催化前複合物B complex狀態（pre-B complex ）和B complex狀態（pre-catalytic spliceosome）的剪接體電鏡結構。清華大學白蕊、萬蕊雪和閆創業該文的共同第一作者，施一公教授為本文的通訊作者。
在剪接反應過程中，多種蛋白質-核酸複合物及剪接因子按照高度精確的順序發生結合和解聚，依次形成預組裝複合物U4/U6.U5 tri-snRNP以及至少7個狀態的組裝剪接體B、Bact、B*、C、C*、P以及ILS複合物。
早在2015年8月，施一公課題組就在Science上背靠背地發表兩篇研究長文，報道了裂殖酵母3.6 Å分辨率下的內含子套索剪切體ILS complex的冷凍電鏡結構，揭示了剪接體剪接活性位點的原子詳情和總的蛋白和RNA的組織形式，並闡釋了剪切體對pre-mRNA進行剪接的基本工作原理。此後，施一公教授課題組與MRC分子生物學實驗室Nagai研究組、德國馬普生物物理化學研究所Reinhard Lüehrmann教授一起互補或背靠背地解析了釀酒酵母或人源的預組裝複合物U4/U6.U5 tri-snRNP、催化前複合物B complex、激活狀態複合物Bact complex、第一步催化反應複合物C complex、第二步催化激活狀態下的C* complex、內含子套索剪接體ILS complex以及剪接體呈現RNA剪接反應完成後狀態P complex的三維結構。
釀酒酵母 pre-B complex 和 B complex狀態下剪接體電鏡結構
附施一公實驗室有關剪接體的論文列表：
1、Yan, C., Hang, J., Wan, R., Huang, M., Wong, C. C., & Shi, Y. (2015). Structure of a yeast spliceosome at 3.6-angstrom resolution. Science, 349(6253), 1182-1191.
2、Hang, J., Wan, R., Yan, C., & Shi, Y. (2015). Structural basis of pre-mRNA splicing. Science, 349(6253), 1191-1198.
3、Wan, R., Yan, C., Bai, R., Wang, L., Huang, M., Wong, C. C., & Shi, Y. (2016). The 3.8 Å structure of the U4/U6. U5 tri-snRNP: Insights into spliceosome assembly and catalysis. Science, 351(6272), 466-475.
4、Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast activated spliceosome at 3.5 Å resolution.Science, 353(6302), 904-911.
5、Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast step II catalytically activated spliceosome.Science, aak9979.
6、Wan, R., Yan, C., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution.Science, 353(6302), 895-904.
7、Zhang, X., Yan, C., Hang, J.,Finci, L., Lei, J., & Shi, Y. (2017).An Atomic Structure of the Human Spliceosome.Cell，169, 1–12
8、Wan, R., Yan, C., Bai, R.,Lei, J., & Shi, Y. (2017).Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae.Cell，171, 1–13
9、Bai, R., Yan, C., Wan, R., Lei, J., & Shi, Y. (2017). Structure of the Post-catalytic Spliceosome from Saccharomyces cerevisiae. Cell, 171(7), 1589-1598.
10、Zhan, X., Yan, C., Zhang, X., Lei, J., & Shi, Y. (2018). Structure of a human catalytic step I spliceosome. Science , eaar6401.
綜述：
Shi, Y. (2017). Mechanistic insights into precursor messenger RNA splicing by the spliceosome. Nature Reviews Molecular Cell Biology.
Shi, Y. (2017). The Spliceosome: A Protein-Directed Metalloribozyme. Journal of Molecular Biology, 429(17), 2640-2653.
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