Prespliceosome structure provides insights into spliceosome assembly and regulation.
Prespliceosome structure provides insights into spliceosome assembly and regulation.
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DOI：
10.1038/s41586-018-0323-8
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发表时间：
2018-07
期刊：
影响因子：
64.8
通讯作者：
Nagai K
中科院分区：
文献类型：
--
作者：
Plaschka C;Lin PC;Charenton C;Nagai K
The spliceosome catalyzes the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors. For branching, the intron 5'-splice site (5'SS) and the branch point (BP) sequence are selected and brought into the prespliceosome by the U1 and U2 snRNPs, which is a focal point for the regulation by alternative splicing factors. The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome. Recent studies have revealed the structural basis of the branching and exon-ligation reactions. However, the structural basis of early spliceosome assembly events remains poorly understood. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae prespliceosome at near-atomic resolution. The structure reveals an induced stabilization of the 5'SS in the U1 snRNP, and provides structural insights into the functions of the human alternative splicing factors LUC7-like (yeast Luc7) and TIA-1 (yeast Nam8) that are linked to human disease. In the prespliceosome, the U1 snRNP associates with the U2 snRNP through a stable contact with the U2 3' domain and a transient yeast-specific contact with the U2 SF3b-containing 5' region, leaving its tri-snRNP-binding interface fully exposed. The results suggest mechanisms for 5'SS transfer to the U6 ACAGAGA region within the assembled spliceosome and for its subsequent conversion to the activation-competent B complex spliceosome. Taken together, the data provide a working model to investigate the early steps of spliceosome assembly.
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影响因子：
48
作者：
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通讯作者：
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DOI：
10.1261/rna.042838.113
发表时间：
2014-05
期刊：
RNA (New York, N.Y.)
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
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