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YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance

Hongna Zuo1,2, Jin Liu1,2, Bin Shen3

  • 1Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Cell Death Discovery
|October 16, 2024
PubMed

Insights

The nuclear protein YTHDC1 is crucial for maintaining hematopoietic stem cell (HSC) function and self-renewal by regulating microRNA maturation. Its absence leads to HSC loss, highlighting the YTHDC1-HP1BP3-microRNA axis

Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • RNA Biology

Background:

  • N6-methyladenosine (m6A) modifications regulate RNA metabolism.
  • YTHDC1 is an m6A reader protein.
  • The role of YTHDC1 in hematopoietic stem cell (HSC) homeostasis is not fully understood.

Purpose of the Study:

  • Investigate the function of YTHDC1 in normal hematopoiesis and HSC maintenance.
  • Elucidate the mechanisms by which YTHDC1 regulates HSCs.

Main Methods:

  • Utilized conditional Ythdc1 knockout mice and Ythdc1/Mettl3 double knockout mice.
  • Analyzed HSC maintenance, self-renewal, and apoptosis.
  • Examined microRNA maturation and levels.
  • Investigated protein interactions, specifically YTHDC1 with HP1BP3.

Main Results:

  • YTHDC1 is essential for HSC maintenance and self-renewal in vivo.
  • YTHDC1 deficiency leads to HSC apoptosis and altered microRNA levels.
  • YTHDC1 interacts with HP1BP3, a nuclear RNA binding protein involved in microRNA maturation.
  • Overexpression of specific microRNAs partially rescued YTHDC1-null HSC defects.

Conclusions:

  • The YTHDC1-HP1BP3-microRNA maturation axis is vital for long-term HSC maintenance.
  • YTHDC1 plays a critical role in regulating hematopoiesis through microRNA pathways.

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