[Research Article] Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution
Each cycle of pre–messenger RNA splicing, carried out by the spliceosome, comprises two sequential transesterification reactions, which result in the removal of an intron and the joining of two exons. Here we report an atomic structure of a catalytic step I spliceosome (known as the C complex) from Saccharomyces cerevisiae, as determined by cryo–electron microscopy at an average resolution of 3.4 angstroms. In the structure, the 2′-OH of the invariant adenine nucleotide in the branch point sequence (BPS) is covalently joined to the phosphate at the 5′ end of the 5′ splice site (5′SS), forming an intron lariat. The freed 5′ exon remains anchored to loop I of U5 small nuclear RNA (snRNA), and the 5′SS and BPS of the intron form duplexes with conserved U6 and U2 snRNA sequences, respectively. Specific placement of these RNA elements at the catalytic cavity of Prp8 is stabilized by 15 protein components, including...