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Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development

Jeongwoo Kwon1, Yu-Jin Jo2, Suk Namgoong3

  • 1Department of Animal Sciences, Chungbuk National University, Gaesin-dong, Cheongju, Chungbuk, 361-763, Republic of Korea.

Scientific Reports
|June 16, 2019
PubMed

Insights

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is vital for early embryonic development by regulating gene transcripts. Its function is linked to METTL3-dependent m6A RNA methylation, impacting cell fate.

Area of Science:

  • Developmental Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is involved in RNA processing, including m6A modification.
  • The specific roles of m6A and hnRNPA2/B1 in early embryonic development remain largely unknown.

Purpose of the Study:

  • To investigate the functional significance of hnRNPA2/B1 in early embryonic development.
  • To elucidate the relationship between hnRNPA2/B1 and m6A modification in embryogenesis.

Main Methods:

  • hnRNPA2/B1 knockdown (KD) experiments in early embryos.
  • RNA sequencing (RNA-Seq) analysis of hnRNPA2/B1 KD blastocysts.
  • Knockdown of METTL3 (N6-Adenosine methyltransferase) and assessment of its effects on embryonic development and hnRNPA2/B1 localization.

Main Results:

  • hnRNPA2/B1 knockdown resulted in delayed and blocked embryonic development post the 4-cell stage.
  • RNA-Seq revealed significant alterations in genes related to transcription, translation, cell cycle, stem cell differentiation, and RNA methylation.
  • Inner cell mass markers (OCT4, SOX2) decreased, while a differentiation marker (GATA4) also decreased in hnRNPA2/B1 KD blastocysts.
  • METTL3 knockdown mimicked developmental defects seen in hnRNPA2/B1 KD embryos, with altered hnRNPA2/B1 localization and reduced m6A levels.

Conclusions:

  • hnRNPA2/B1 is essential for early embryogenesis, regulating transcription factors and cell fate.
  • METTL3-dependent m6A RNA methylation plays a crucial role in regulating hnRNPA2/B1 function during embryonic development.

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