Scholarlink

<p>Telomeres are found at the ends of chromosomes, and telomere length correlates with cancer development. Telomeres are extended by telomerase and the alternative lengthening of telomeres pathway in cancer cells. Telomeric repeat-containing RNA (TERRA) is transcribed from telomeres and affects both modes of telomere extension. Telomere DNA and TERRA form the G-quadruplex (G4). The correlation between these noncanonical nucleic acid structures and the transcriptional regulation of TERRA is unclear. We found that the Ewing sarcoma (EWS) binds G4 of telomere DNA and TERRA competitively in vitro. In cells, the binding of EWS to telomeres was dependent on the Arg–Gly–Gly (RGG) domain at the C-terminal region, promoting H3K27Ac enrichment at the telomeric region depending on the N-terminal region. EWS promoted TERRA transcription; however, an EWS mutant with a deleted RGG domain or N-terminal region did not. These findings indicate that EWS promotes TERRA transcription. Compared with EWS overexpression, overexpression of mutant EWS in which native RGG was substituted with RGGF, only bound G4 DNA and not G4 RNA, significantly increasing the transcript level of TERRA. These findings suggest that competitive binding of TERRA and telomeric DNA to EWS maintains the level of TERRA transcripts.</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

Transcriptional regulation of telomeric repeat-containing RNA by the G-quadruplex-binding Ewing sarcoma protein

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月27日

查看全文
  • Luthfi Lulul Ulum,
  • Wakana Matsudaira,
  • Maiko Yamanashi,
  • Natsuki Shibata,
  • Showmitra Saha,
  • Akinori Ishihara,
  • Takanori Oyoshi

摘要

Telomeres are found at the ends of chromosomes, and telomere length correlates with cancer development. Telomeres are extended by telomerase and the alternative lengthening of telomeres pathway in cancer cells. Telomeric repeat-containing RNA (TERRA) is transcribed from telomeres and affects both modes of telomere extension. Telomere DNA and TERRA form the G-quadruplex (G4). The correlation between these noncanonical nucleic acid structures and the transcriptional regulation of TERRA is unclear. We found that the Ewing sarcoma (EWS) binds G4 of telomere DNA and TERRA competitively in vitro. In cells, the binding of EWS to telomeres was dependent on the Arg–Gly–Gly (RGG) domain at the C-terminal region, promoting H3K27Ac enrichment at the telomeric region depending on the N-terminal region. EWS promoted TERRA transcription; however, an EWS mutant with a deleted RGG domain or N-terminal region did not. These findings indicate that EWS promotes TERRA transcription. Compared with EWS overexpression, overexpression of mutant EWS in which native RGG was substituted with RGGF, only bound G4 DNA and not G4 RNA, significantly increasing the transcript level of TERRA. These findings suggest that competitive binding of TERRA and telomeric DNA to EWS maintains the level of TERRA transcripts.