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

Research output: Contribution to journalArticle

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

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Long Noncoding RNA
Oncogenes
Tumors
DNA
Activity Cycles
Systems Biology
Supercomputers
Tumor Suppressor Genes
Proteomics
Cell Cycle
Carrier Proteins
Genes
Cells
Neoplasms

All Science Journal Classification (ASJC) codes

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

Cite this

Kajino, T., Shimamura, T., Gong, S., Yanagisawa, K., Ida, L., Nakatochi, M., ... 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
Kajino, Taisuke ; Shimamura, Teppei ; Gong, Shuyi ; Yanagisawa, Kiyoshi ; Ida, Lisa ; Nakatochi, Masahiro ; Griesing, Sebastian ; Shimada, Yukako ; Kano, Keiko ; Suzuki, Motoshi ; Miyano, Satoru ; Takahashi, Takashi. / Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. In: EMBO Journal. 2019 ; Vol. 38, No. 17.
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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.",
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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, vol. 38, no. 17, e98441. https://doi.org/10.15252/embj.201798441

Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. / Kajino, Taisuke; Shimamura, Teppei; Gong, Shuyi; Yanagisawa, Kiyoshi; Ida, Lisa; Nakatochi, Masahiro; Griesing, Sebastian; Shimada, Yukako; Kano, Keiko; Suzuki, Motoshi; Miyano, Satoru; Takahashi, Takashi.

In: EMBO Journal, Vol. 38, No. 17, e98441, 02.09.2019.

Research output: Contribution to journalArticle

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AU - Kajino, Taisuke

AU - Shimamura, Teppei

AU - Gong, Shuyi

AU - Yanagisawa, Kiyoshi

AU - Ida, Lisa

AU - Nakatochi, Masahiro

AU - Griesing, Sebastian

AU - Shimada, Yukako

AU - Kano, Keiko

AU - Suzuki, Motoshi

AU - Miyano, Satoru

AU - Takahashi, Takashi

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Kajino T, Shimamura T, Gong S, Yanagisawa K, Ida L, Nakatochi M et al. Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. EMBO Journal. 2019 Sep 2;38(17). e98441. https://doi.org/10.15252/embj.201798441