Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome

• 成果类型: Article
• 署名作者: Bai, Rui; Yuan, Meng; Zhang, Pu; Luo, Ting; Shi, Yigong; Wan, Ruixue
• 署名单位: Westlake University; Westlake Laboratory; Westlake University; Tsinghua University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13468
• DOI: 10.1126/science.adn7272
• 发表日期: 2024-03-15
• 页码: 1245-1252
• 关键词: small nuclear ribonucleoproteins; cryo-em structure; crystal-structure; u12 snrna; human u4/u6.u5; protein; rna; Visualization; requirement; RESOLUTION

摘要

The minor spliceosome, which is responsible for the splicing of U12-type introns, comprises five small nuclear RNAs (snRNAs), of which only one is shared with the major spliceosome. In this work, we report the 3.3-angstrom cryo-electron microscopy structure of the fully assembled human minor spliceosome pre-B complex. The atomic model includes U11 small nuclear ribonucleoprotein (snRNP), U12 snRNP, and U4atac/U6atac.U5 tri-snRNP. U11 snRNA is recognized by five U11-specific proteins (20K, 25K, 35K, 48K, and 59K) and the heptameric Sm ring. The 3 ' half of the 5 '-splice site forms a duplex with U11 snRNA; the 5 ' half is recognized by U11-35K, U11-48K, and U11 snRNA. Two proteins, CENATAC and DIM2/TXNL4B, specifically associate with the minor tri-snRNP. A structural analysis uncovered how two conformationally similar tri-snRNPs are differentiated by the minor and major prespliceosomes for assembly.