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Updated: Feb 4, 2026

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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RBM15B recognizes H3K79me2 to guide selective m6A-modification of mRNA and enhance oncoprotein translation in MLL-r

Tian-Qi Chen1, Yu-Meng Sun1, Shun-Xin Zhu1

  • 1MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 510275, Guangzhou, China.

The EMBO Journal
|February 2, 2026
PubMed

Insights

This study reveals how H3K79me2 histone methylation guides RBM15B to deposit N6-methyladenosine (m6A) on RNA. This epigenetic mechanism promotes leukemia by enhancing oncogenic transcript translation and leukemic stem cell survival.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • N6-methyladenosine (m6A) RNA modification regulates gene expression and is implicated in various biological processes.
  • The mechanisms of site-selective m6A deposition, particularly in start codon regions, and its role in tumorigenesis are not well understood.

Purpose of the Study:

  • To elucidate the mechanism of site-selective m6A deposition guided by epigenetic modifications.
  • To investigate the role of the H3K79me2-RBM15B axis in hematological malignancies.

Main Methods:

  • Identification of RBM15B as a key modulator of m6A modification in 5'UTRs and near start codons.
  • Demonstration of H3K79me2 histone methylation guiding RBM15B binding and m6A deposition.
  • Analysis of the functional consequences of the H3K79me2-RBM15B-m6A axis in leukemia.

Main Results:

  • RBM15B selectively deposits m6A guided by H3K79me2, with H47 of RBM15B crucial for H3K79me2 recognition.
  • The H3K79me2-RBM15B-m6A pathway enhances translation of oncogenic transcripts.
  • This axis promotes leukemic stem cell self-renewal and leukemia maintenance.

Conclusions:

  • A novel mechanism for site-selective m6A deposition mediated by H3K79me2 and RBM15B is uncovered.
  • Targeting the H3K79me2-RBM15B-m6A axis inhibits leukemia cell survival and differentiation.
  • This pathway represents a promising therapeutic target for hematological malignancies.
Keywords:
H3K79me2N6-methyladenosineRBM15BTranslation

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