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Updated: Nov 4, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
08:56

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

11.1K

N6-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic

Yuanming Cheng1, Wei Xie2, Brian F Pickering3

  • 1Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Cancer Cell
|May 28, 2021
PubMed

Insights

Nuclear m6A condensates (nYACs) are essential for acute myeloid leukemia (AML) cell survival and differentiation. YTHDC1 protein forms these condensates, protecting mRNA from degradation and maintaining leukemia progression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • N6-Methyladenosine (m6A) modification on mRNAs regulates biological processes.
  • Dysregulation of m6A is implicated in tumorigenesis, but its role in leukemia is unclear.

Purpose of the Study:

  • To investigate the role of m6A and its readers in myeloid leukemia.
  • To elucidate the molecular mechanisms by which m6A influences leukemia cell biology.

Main Methods:

  • Genome-wide CRISPR screen to identify essential m6A readers.
  • Analysis of nuclear YTHDC1-m6A condensates (nYACs) in leukemia cells.
  • Investigation of YTHDC1's role in mRNA stability and degradation pathways.

Main Results:

  • YTHDC1 was identified as a critical m6A reader in myeloid leukemia.
  • m6A facilitates YTHDC1 liquid-liquid phase separation, forming nYACs, which are increased in AML cells.
  • nYACs are crucial for AML cell survival, maintaining an undifferentiated state, and protecting m6A-mRNAs from degradation by the PAXT complex and exosome.

Conclusions:

  • m6A is essential for forming phase-separated nuclear bodies (nYACs) that maintain mRNA stability.
  • These nYACs are critical for controlling cancer cell survival and differentiation in leukemia.
Keywords:
RNA methylationRNA-binding proteinsdifferentiationmyeloid leukemiaphase separation

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