Journal: Science / Year: 2018 Title: Structure of a human catalytic step I spliceosome. Authors: Xiechao Zhan / Chuangye Yan / Xiaofeng Zhang / Jianlin Lei / Yigong Shi / 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 ...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 C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in , 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.
A: Pre-mRNA-processing-splicing factor 8 B: U5 snRNA C: 116 kDa U5 small nuclear ribonucleoprotein component D: U5 small nuclear ribonucleoprotein 200 kDa helicase E: U5 small nuclear ribonucleoprotein 40 kDa protein F: U6 snRNA G: Pre-mRNA H: U2 snRNA I: Pre-mRNA-splicing factor SYF1 J: Crooked neck-like protein 1 K: Pre-mRNA-splicing factor SPF27 L: Cell division cycle 5-like protein y: Pre-mRNA-splicing factor ISY1 homolog M: Pre-mRNA-splicing factor SYF2 N: Protein BUD31 homolog O: Pre-mRNA-splicing factor RBM22 P: Spliceosome-associated protein CWC15 homolog R: SNW domain-containing protein 1 S: Peptidyl-prolyl cis-trans isomerase-like 1 T: Pleiotropic regulator 1 Q: Intron-binding protein aquarius U: Serine/arginine repetitive matrix protein 2 V: Pre-mRNA-splicing factor CWC22 homolog W: Pre-mRNA-processing factor 17 X: Pre-mRNA-splicing factor CWC25 homolog Y: Coiled-coil domain-containing protein 94 Z: Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 q: Pre-mRNA-processing factor 19 r: Pre-mRNA-processing factor 19 s: Pre-mRNA-processing factor 19 t: Pre-mRNA-processing factor 19 u: Eukaryotic initiation factor 4A-III v: Protein mago nashi homolog 2 w: RNA-binding protein 8A x: Protein CASC3 h: Small nuclear ribonucleoprotein Sm D3 i: Small nuclear ribonucleoprotein-associated proteins B and B' j: Small nuclear ribonucleoprotein Sm D1 k: Small nuclear ribonucleoprotein Sm D2 m: Small nuclear ribonucleoprotein F l: Small nuclear ribonucleoprotein E n: Small nuclear ribonucleoprotein G o: U2 small nuclear ribonucleoprotein A' p: U2 small nuclear ribonucleoprotein B'' a: Small nuclear ribonucleoprotein Sm D3 b: Small nuclear ribonucleoprotein-associated proteins B and B' c: Small nuclear ribonucleoprotein Sm D1 d: Small nuclear ribonucleoprotein Sm D2 f: Small nuclear ribonucleoprotein F e: Small nuclear ribonucleoprotein E g: Small nuclear ribonucleoprotein G 1: Peptidyl-prolyl cis-trans isomerase E 2: Peptidylprolyl isomerase domain and WD repeat-containing protein 1 3: Peptidyl-prolyl cis-trans isomerase G 4: UNKNOW hetero molecules
Mass: 46930.961 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P38919, RNA helicase
#30: Protein
Proteinmagonashihomolog2
Mass: 17301.799 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96A72
#31: Protein
RNA-bindingprotein8A / Binder of OVCA1-1 / BOV-1 / RNA-binding motif protein 8A / RNA-binding protein Y14 / Ribonucleoprotein RBM8A
Mass: 19925.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y5S9
#32: Protein
ProteinCASC3 / Cancer susceptibility candidate gene 3 protein / Metastatic lymph node gene 51 protein / MLN 51 / ...Cancer susceptibility candidate gene 3 protein / Metastatic lymph node gene 51 protein / MLN 51 / Protein barentsz / Btz
Mass: 76381.992 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15234
#34: Protein
Smallnuclearribonucleoprotein-associatedproteinsBandB' / snRNP-B / Sm protein B/B' / SmB/B'
Mass: 23459.688 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P14678
Pre-mRNA-splicingfactorSYF1 / Protein HCNP / XPA-binding protein 2
Mass: 100148.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9HCS7
#11: Protein
Pre-mRNA-splicingfactorSPF27 / Breast carcinoma-amplified sequence 2 / DNA amplified in mammary carcinoma 1 protein / Spliceosome- ...Breast carcinoma-amplified sequence 2 / DNA amplified in mammary carcinoma 1 protein / Spliceosome-associated protein SPF 27
Mass: 26163.420 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O75934
#13: Protein
Pre-mRNA-splicingfactorISY1homolog
Mass: 35499.074 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9ULR0