Scholarlink

<p>Intron removal during pre-mRNA splicing is of extraordinary complexity and its disruption causes a vast number of genetic diseases in humans. While key steps of the canonical spliceosome cycle have been revealed by combined structure–function analyses, structural information on an aberrant spliceosome committed to premature disassembly is not available. Here, we report two cryo-electron microscopy structures of post-B<sup>act</sup> spliceosome intermediates from <i>Schizosaccharomyces</i> <i>pombe</i> primed for disassembly. We identify the DEAH-box helicase–G-patch protein pair (Gih35–Gpl1, homologous to human DHX35–GPATCH1) and show how it maintains catalytic dormancy. In both structures, Gpl1 recognizes a remodeled active site introduced by an overstabilization of the U5 loop I interaction with the 5′ exon leading to a single-nucleotide insertion at the 5′ splice site. Remodeling is communicated to the spliceosome surface and the Ntr1 complex that mediates disassembly is recruited. Our data pave the way for a targeted analysis of splicing quality control.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structures of aberrant spliceosome intermediates on their way to disassembly

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月20日

查看全文
  • Komal Soni,
  • Attila Horvath,
  • Olexandr Dybkov,
  • Merlin Schwan,
  • Sasanan Trakansuebkul,
  • Dirk Flemming,
  • Klemens Wild,
  • Henning Urlaub,
  • Tamás Fischer,
  • Irmgard Sinning

摘要

Intron removal during pre-mRNA splicing is of extraordinary complexity and its disruption causes a vast number of genetic diseases in humans. While key steps of the canonical spliceosome cycle have been revealed by combined structure–function analyses, structural information on an aberrant spliceosome committed to premature disassembly is not available. Here, we report two cryo-electron microscopy structures of post-Bact spliceosome intermediates from Schizosaccharomyces pombe primed for disassembly. We identify the DEAH-box helicase–G-patch protein pair (Gih35–Gpl1, homologous to human DHX35–GPATCH1) and show how it maintains catalytic dormancy. In both structures, Gpl1 recognizes a remodeled active site introduced by an overstabilization of the U5 loop I interaction with the 5′ exon leading to a single-nucleotide insertion at the 5′ splice site. Remodeling is communicated to the spliceosome surface and the Ntr1 complex that mediates disassembly is recruited. Our data pave the way for a targeted analysis of splicing quality control.