真核生物pre-mRNA剪接由超分子複合物剪接體（spliceosome）完成。完整的剪接過程主要分爲八種不同的狀態，預催化剪接體的前體（pre-B），預催化剪接體（B），活化複合物（Bact），催化活化複合物（B*），催化步驟I複合物 （C），催化步驟II活化複合物（C*），催化後剪接體（P）和內含子套索剪接體（ILS）。

自2015年第一個近原子分辨率、來自S. pombe的剪接體結構通過Cryo-EM技術被解析以來，已經陸續有多個不同狀態的剪接體被解析。其中有13個分辨率在3.3-5.8 Å之間的酵母剪接體和11個人源剪接體已經被解析，這些剪接體分佈在催化過程中的七種狀態中。在此之前，只剩下B*複合物結構尚未被解析。

2019年3月14日，Cell 雜誌在線online了來自施一公課題組（萬蕊雪和白蕊爲共同第一作者）關於酵母剪接體的研究長文，題爲Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching。這篇文章報道了2.9–3.8 Å酵母剪接體的B*複合物Cryo-EM結構，完成了剪接催化過程中幾個主要步驟的最後一塊拼圖。

在這項研究中，施一公課題組組裝了來自釀酒酵母的含有兩種不同的pre-mRNA的B*複合物，其中在ACT1 pre-mRNA上組裝的B*複合物平均分辨率2.9 Å；在UBC4 pre-mRNA上組裝的B*複合物平均分辨率3.2 Å。對於這兩種不同的B*複合物中的每一種，又觀察到了兩種不同的構象狀態（圖1 A和B）。不同pre-mRNA上的這些結構揭示了在主要功能狀態下剪接體的底物特異性構象，爲揭示對branching反應的機理提供了重要參考。

圖1. 酵母中B*複合物結構

原文鏈接：

https://doi.org/10.1016/j.cell.2019.02.006

附施一公實驗室有關剪接體的論文列表：

1.Yan, C. et al. Structure of a yeast spliceosome at 3.6-angstrom resolution. Science 349, 1182-1191 (2015).

2.Hang, J., Wan, R., Yan, C. & Shi, Y. Structural basis of pre-mRNA splicing. Science 349, 1191-1198 (2015).

3. Wan, R. et al. The 3.8 Å structure of the U4/U6. U5 tri-snRNP: Insights into spliceosome assembly and catalysis. Science, aad6466 (2016).

4. Yan, C., Wan, R., Bai, R., Huang, G. & Shi, Y. Structure of a yeast activated spliceosome at 3.5 Å resolution. Science 353, 904-911 (2016).

5. Wan, R., Yan, C., Bai, R., Huang, G. & Shi, Y. Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution. Science 353, 895-904 (2016).

6.Yan, C., Wan, R., Bai, R., Huang, G. & Shi, Y. Structure of a yeast step II catalytically activated spliceosome. Science 355, 149-155 (2017).

7.Zhang, X. et al. An atomic structure of the human spliceosome. Cell 169, 918-929. e914 (2017).

8.Wan, R., Yan, C., Bai, R., Lei, J. & Shi, Y. Structure of an intron lariat spliceosome from Saccharomyces cerevisiae. Cell 171, 120-132. e112 (2017).

9. Bai, R., Yan, C., Wan, R., Lei, J. & Shi, Y. Structure of the post-catalytic spliceosome from Saccharomyces cerevisiae. Cell 171, 1589-1598. e1588 (2017).

10. Shi, Y. Mechanistic insights into precursor messenger RNA splicing by the spliceosome. Nature Reviews Molecular Cell Biology 18, 655 (2017).

11.Shi, Y. The spliceosome: a protein-directed metalloribozyme. Journal of molecular biology 429, 2640-2653 (2017).

12. Zhan, X., Yan, C., Zhang, X., Lei, J. & Shi, Y. Structure of a human catalytic step I spliceosome.Science 359, 537-545 (2018).

13. Bai, R., Wan, R., Yan, C., Lei, J. & Shi, Y. Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation. Science, eaau0325 (2018).

14. Zhang, X. et al. Structures of the human spliceosomes before and after release of the ligated exon. Cell research, 1 (2019).

15. Yan, C., Wan, R. & Shi, Y. Molecular mechanisms of pre-mRNA splicing through structural biology of the spliceosome. Cold Spring Harbor perspectives in biology 11, a032409 (2019).

16. Wan, R., Bai, R., Yan, C., Lei, J. & Shi, Y. Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching. Cell (2019).