Pre-mRNA splicing, the removal of introns from mRNA precursors, is a dynamic process and requires many conformational rearrangements (1). It is catalyzed by the spliceosome, which is a large machine formed by ordered interactions of several small nuclear ribonucleoproteins (snRNPs), 3 U1, U2, U5, and U4/U6, and numerous other less stably associated nonsnRNP splicing factors (2). The assembly of the spliceosome goes through many intermediate stages. The stable intermediate complexes are the A, B, and C complexes. After the complex A is formed by pre-mRNA binding to the U1 and U2, it recruits U4/U6⅐U5 tri-snRNP, forming the B complex. The B complex is still inactive and requires conformational and compositional rearrangements to form active spliceosome, complex B* (3). Complex B* undergoes the first catalytic step of splicing to generate complex C. After additional rearrangements occur in the spliceosomal RNP network (4), complex C undergoes a second catalytic step and releases the mRNA.Mass spectrometric analyses of the human A (5), B (6, 7), B* (8), and C (7) complexes indicate that there are dramatic changes in protein content during splicing. For example, in the A complex to B complex transition, ϳ25 proteins are recruited and more than 35 non-snRNP proteins associated. These include the Prp19⅐CDC5 complex and Prp19-related factors. Subunits of these become more stably integrated in the B* complex (8, 9). Recently, Bessonov et al. (7) purified the catalytically active C complex and identified its stable RNP core, which constituted with Prp19⅐CDC5 and Prp19-related factors. Ski interaction protein (SKIP) and peptidylprolyl isomerase-like protein 1 (PPIL1) belong to Prp19-related factors and are included in this stable RNP core. Both of them are believed to be involved in the activation of the spliceosome (2,8,9).Human SKIP (536 residues) is colocalized with SC35, a splicing factor at nuclear speckles (11). Expression of a dominant negative SKIP (residues 87-342 of SKIP) results in a 1,25-(OH) 2 D 3 -dependent transient accumulation of the unspliced transcripts (12), indicting that SKIP influences pre-mRNA splicing. Nagai et al. (13) reported that SKIP affected the splicing of a natural gene product, the downstream intron, and aber-* This work was supported by the Chinese National Fundamental Research Project (Grants 2006CB806507, 2006CB910201, 2002CB713806, and 2006AA02A315) and the Chinese National Natural Science Foundation (Grants 30121001, 30570361, and 30830031
