Scholarlink

<p>Gene duplication generates gene paralogs that may undergo diverse fates during evolution, and thus serves as a potent catalyst of biological complexity. Genetic paralogs frequently share redundant functions and may also exhibit antagonistic activities by competing for common interaction partners. Here we show that the gene paralogs <i>NRBP1</i> and <i>NRBP2</i> oppositely regulate long interspersed nuclear element-1 (L1) retrotransposition, via influencing integrity of the L1 ribonucleoprotein complex. We demonstrate that the opposing roles of NRBP1 and NRBP2 are not results of a competitive mechanism, but rather due to targeting NRBP1 for degradation by NRBP2, probably through heterodimer formation. Moreover, our phylogenetic analysis shows that the regulatory function of NRBP2 may be acquired later during evolution, suggesting that evolutionary pressure has favored this functional fine-tuning of NRBP1. In summary, our findings not only identify NRBP1/2 as L1 regulators and implicate their involvement in human pathogenesis, but also provide a mechanistic insight into the regulatory details arising from gene duplication.</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

Opposing roles of pseudokinases NRBP1 and NRBP2 in regulating L1 retrotransposition

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月11日

查看全文
  • Wei Yang,
  • Shaobo Cong,
  • Ruoyao Li,
  • Jennifer Schwarz,
  • Thilo Schulze,
  • Raban A. Gevelhoff,
  • Xinyan Chen,
  • Sara Ullrich,
  • Kristina Falkenstein,
  • Denis Ott,
  • Pia Eixmann,
  • Angelica Trentino,
  • Antje Thien,
  • Thierry Heidmann,
  • Ekkehard Schulze,
  • Bettina Warscheid,
  • Ralf Baumeister,
  • Wenjing Qi

摘要

Gene duplication generates gene paralogs that may undergo diverse fates during evolution, and thus serves as a potent catalyst of biological complexity. Genetic paralogs frequently share redundant functions and may also exhibit antagonistic activities by competing for common interaction partners. Here we show that the gene paralogs NRBP1 and NRBP2 oppositely regulate long interspersed nuclear element-1 (L1) retrotransposition, via influencing integrity of the L1 ribonucleoprotein complex. We demonstrate that the opposing roles of NRBP1 and NRBP2 are not results of a competitive mechanism, but rather due to targeting NRBP1 for degradation by NRBP2, probably through heterodimer formation. Moreover, our phylogenetic analysis shows that the regulatory function of NRBP2 may be acquired later during evolution, suggesting that evolutionary pressure has favored this functional fine-tuning of NRBP1. In summary, our findings not only identify NRBP1/2 as L1 regulators and implicate their involvement in human pathogenesis, but also provide a mechanistic insight into the regulatory details arising from gene duplication.