Journal Article

Structure of a human catalytic step I spliceosome

Zhan, Xiechao, Shi, Yigong, Lei, Jianlin, Yan, Chuangye, Zhang, Xiaofeng

2018

Overview

Catalyzed by the spliceosome, precursor mRNA splicing proceeds in two steps: branching and exon ligation. Transition from the C (catalytic post-branching spliceosome) to the C* (catalytic pre-exon ligation spliceosome) complex is driven by the adenosine triphosphatase/helicase Prp16. Zhan et al. report the cryo-electron microscopy structure of the human C complex, showing that two step I splicing factors stabilize the active site and link it to Prp16. Science , this issue p. 537 The cryo–electron microscopy structure of the human C complex spliceosome reveals mechanistic insights into ribonucleoprotein remodeling. 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.

• Publisher: The American Association for the Advancement of Science
• Subject: Adenosine / Adenosine triphosphatase / Amino Acid Sequence / Biocatalysis / Catalysis / Catalytic Domain / Cryoelectron Microscopy / DEAD-box RNA Helicases - chemistry / DEAD-box RNA Helicases - ultrastructure / DNA helicase / Electron microscopy / Fungi / Humans / Microscopy / Models, Molecular / mRNA / Proteins / Ribonucleic acid / RNA / RNA Splicing / RNA Splicing Factors - chemistry / RNA Splicing Factors - ultrastructure / Saccharomyces cerevisiae / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - ultrastructure / Spliceosomes - chemistry / Spliceosomes - ultrastructure / Splicing / Splicing factors / Triphosphatase