Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction

Taisuke Kajino, Teppei Shimamura, Shuyi Gong, Kiyoshi Yanagisawa, Lisa Ida, Masahiro Nakatochi, Sebastian Griesing, Yukako Shimada, Keiko Kano, Motoshi Suzuki, Satoru Miyano, Takashi Takahashi

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3 Citations (Scopus)

Abstract

Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.

Original languageEnglish
Article numbere98441
JournalEMBO Journal
Volume38
Issue number17
DOIs
Publication statusPublished - 02-09-2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Kajino, T., Shimamura, T., Gong, S., Yanagisawa, K., Ida, L., Nakatochi, M., Griesing, S., Shimada, Y., Kano, K., Suzuki, M., Miyano, S., & Takahashi, T. (2019). Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. EMBO Journal, 38(17), [e98441]. https://doi.org/10.15252/embj.201798441