Scholarlink

<p>RNA binding proteins could regulate transcription through modulating RNA polymerase II involved transcriptional condensates with the aid of nascent RNA. However, whether this mechanism also contributes to tumorigenesis is still unknown. Here, we show the RBP AKAP95 is required for MLL rearranged leukemogenesis. Phase separation and RNA binding properties of AKAP95 modulate Pol II recruitment into condensates at genome-wide target sites. AKAP95 interact with MLL1 translocated fragment and their partial co-condensation leads to stronger AKAP95 binding towards MLL-AF9 target genes. Loss of AKAP95 significantly downregulates expression of MLL-AF9 targets and impairs MLL-AF9 driven leukemogenesis. AKAP95 is not essential for normal and regenerative hematopoiesis, rendering it an ideal target for leukemia therapeutics. As an endeavor for modifying condensates, we design a peptide JD-PI95 bridging AKAP95 to protein quality surveillance component HSP70. The peptide successfully impairs AKAP95 phase separation, attenuates gene transcription and inhibits <i>MLL</i>r leukemia cells proliferation. Our work demonstrates an important role of RBP condensates in tumorigenesis through regulation of transcription and a new method to perturb specific condensates for tumor inhibition.</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

AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月7日

查看全文
  • Xiang Yan,
  • Yongkun Luan,
  • Yi Zhu,
  • You Cai,
  • Fanghua Ye,
  • Liangchun Yang,
  • Kaibo Zhu,
  • Jing Hu,
  • Shuangzi Luo,
  • Jiazheng Lin,
  • Yixiu Wang,
  • Yulu Huang,
  • Ping Sun,
  • Zhenhua Yang,
  • Bi Shi,
  • Hao Jiang,
  • Wei Li

摘要

RNA binding proteins could regulate transcription through modulating RNA polymerase II involved transcriptional condensates with the aid of nascent RNA. However, whether this mechanism also contributes to tumorigenesis is still unknown. Here, we show the RBP AKAP95 is required for MLL rearranged leukemogenesis. Phase separation and RNA binding properties of AKAP95 modulate Pol II recruitment into condensates at genome-wide target sites. AKAP95 interact with MLL1 translocated fragment and their partial co-condensation leads to stronger AKAP95 binding towards MLL-AF9 target genes. Loss of AKAP95 significantly downregulates expression of MLL-AF9 targets and impairs MLL-AF9 driven leukemogenesis. AKAP95 is not essential for normal and regenerative hematopoiesis, rendering it an ideal target for leukemia therapeutics. As an endeavor for modifying condensates, we design a peptide JD-PI95 bridging AKAP95 to protein quality surveillance component HSP70. The peptide successfully impairs AKAP95 phase separation, attenuates gene transcription and inhibits MLLr leukemia cells proliferation. Our work demonstrates an important role of RBP condensates in tumorigenesis through regulation of transcription and a new method to perturb specific condensates for tumor inhibition.