2. Academic Validation
  3. Structure of a human catalytic step I spliceosome

Structure of a human catalytic step I spliceosome

  • Science. 2018 Feb 2;359(6375):537-545. doi: 10.1126/science.aar6401.
Xiechao Zhan 1,  Chuangye Yan 2,  Xiaofeng Zhang 1,  Jianlin Lei 1 3,  Yigong Shi 2 4
Affiliations

Affiliations

  • 1 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 2 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. yancy05@mails.tsinghua.edu.cn shi-lab@tsinghua.edu.cn.
  • 3 Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 4 Institute of Biology, Westlake Institute for Advanced Study, Westlake University, Shilongshan Road No. 18, Xihu District, Hangzhou 310064, Zhejiang Province, China.
PMID: 29301961 DOI: 10.1126/science.aar6401
Abstract

Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron microscopy structure of the human C complex at an average resolution of 4.1 angstroms. Compared with the Saccharomyces cerevisiae C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in S. cerevisiae, respectively) closely interact with the DEAH-family adenosine triphosphatase/helicase Prp16 and bridge the gap between Prp16 and the active-site RNA elements. These features, together with structural comparison of the human C and C* complexes, provide mechanistic insights into ribonucleoprotein remodeling and allow the proposition of a working mechanism for the C-to-C* transition.

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