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Spliceosome dynamics in the catalytic center
Author(s) -
Tseng Chi-Kang,
Liu Hsueh-Lien,
Cheng Soo-Chen
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.101.1
Subject(s) - spliceosome , rna splicing , chemistry , catalysis , biophysics , stereochemistry , rna , biochemistry , biology , gene
Eight DExD/H‐box proteins are involved in the splicing pathway to mediate structural changes of the spliceosome. Among them, Prp2 and Prp16 are required for the first and second catalytic step, respectively. Recent studies have revealed the function of Prp2 and Prp16 to be associated with the displacement of SF3a/b and Yju2/Cwc25 from the spliceosome. SF3b and Cwc25 bind to the branch site at the pre‐catalytic and the first catalytic step during the splicing reaction. Their removal from the spliceosome may create an open space in the catalytic center, providing structural flexibility to allow repositioning of splice sites, which is facilitated by the binding of Yju2/Cwc25 and Slu7/Prp18/Prp22 for the first and second reaction, respectively. We have found that the affinity‐purified spliceosome arrested at specific stages is highly flexible in its structure and catalytic potentials. Not only both transesterification reactions are reversible, the spliceosome can also catalyze hydrolytic spliced‐exon reopening reaction (SER) and debranching reaction. The mode of the reaction catalyzed by the spliceosome is influenced by the pH, the presence of KCl, the concentration of divalent cation, and also by the structure of Cwc25 and Slu7 that binds to the spliceosome, suggesting that the spliceosome can be directed to catalyze versatile reactions by subtle changes in the conformation of the catalytic center.