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Publication Abstract from PubMed

Spliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron. Most states of the intron-defined spliceosome have been structurally characterized. However, the structure of a fully assembled exon-defined spliceosome remains at large. During spliceosome assembly, the pre-catalytic state (B complex) is converted from its precursor (pre-B complex). Here we report atomic structures of the exon-defined human spliceosome in four sequential states: mature pre-B, late pre-B, early B, and mature B. In the previously unknown late pre-B state, U1 snRNP is already released but the remaining proteins are still in the pre-B state; unexpectedly, the RNAs are in the B state, with U6 snRNA forming a duplex with 5'-splice site and U5 snRNA recognizing the 3'-end of the exon. In the early and mature B complexes, the B-specific factors are stepwise recruited and specifically recognize the exon 3'-region. Our study reveals key insights into the assembly of the exon-defined spliceosomes and identifies mechanistic steps of the pre-B-to-B transition.

Structural insights into human exon-defined spliceosome prior to activation.,Zhang W, Zhang X, Zhan X, Bai R, Lei J, Yan C, Shi Y Cell Res. 2024 Jun;34(6):428-439. doi: 10.1038/s41422-024-00949-w. Epub 2024 Apr , 24. PMID:38658629^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.