Scholarlink

<p>Antigenic variation is an immune evasion strategy used by pathogens, including <i>Trypanosoma brucei</i>. This parasite expresses a single variant surface glycoprotein (VSG) from a large genetic repertoire, which it periodically switches throughout an infection. <i>VSG</i><i>s</i> are co-transcribed with expression-site-associated genes (<i>ESAG</i><i>s</i>) within a specialized nuclear body, but there is substantial differential expression and the regulatory mechanisms remain unclear. Here we applied TurboID-mediated proximity labelling mass spectrometry to map the subnuclear expression-site body (ESB) post-transcriptional network. We identify and characterize three previously undescribed components: ESB-associated protein 1 (ESAP1) and ESB-specific proteins 2 and 3 (ESB2 and 3). These proteins form discreet subnuclear condensates that are developmentally regulated. ESB2 is an active RNA endonuclease that negatively regulates <i>ESAG</i> transcripts. Its recruitment depends on a hierarchy involving VEX2, ESAP1 and ESB3, a constant flux of active transcription and RNA processing, and its own nuclease activity. Overall, we uncover a molecular mechanism that fine-tunes expression of virulence genes through specialized RNA decay in <i>T. brucei</i>.</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

Specialized RNA decay fine-tunes monogenic antigen expression in Trypanosoma brucei

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月30日

查看全文
  • Lianne I. M. Lansink,
  • Htay Mon Aye,
  • Leon Walther,
  • Sophie Longmore,
  • Madeleine Jones,
  • Adam Dowle,
  • João L. Reis-Cunha,
  • Joana R. C. Faria

摘要

Antigenic variation is an immune evasion strategy used by pathogens, including Trypanosoma brucei. This parasite expresses a single variant surface glycoprotein (VSG) from a large genetic repertoire, which it periodically switches throughout an infection. VSGs are co-transcribed with expression-site-associated genes (ESAGs) within a specialized nuclear body, but there is substantial differential expression and the regulatory mechanisms remain unclear. Here we applied TurboID-mediated proximity labelling mass spectrometry to map the subnuclear expression-site body (ESB) post-transcriptional network. We identify and characterize three previously undescribed components: ESB-associated protein 1 (ESAP1) and ESB-specific proteins 2 and 3 (ESB2 and 3). These proteins form discreet subnuclear condensates that are developmentally regulated. ESB2 is an active RNA endonuclease that negatively regulates ESAG transcripts. Its recruitment depends on a hierarchy involving VEX2, ESAP1 and ESB3, a constant flux of active transcription and RNA processing, and its own nuclease activity. Overall, we uncover a molecular mechanism that fine-tunes expression of virulence genes through specialized RNA decay in T. brucei.