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Altering rRNA 2'O-methylation pattern during neuronal differentiation is regulated by FMRP.

Michelle Ninochka D'Souza1,2, Naveen Kumar Chandappa Gowda1,2,3, Nivedita Hariharan2

  • 1Centre for Brain Research, Indian Institute of Science, Bangalore, India.

RNA Biology
|October 3, 2025
PubMed
Summary
This summary is machine-generated.

Fragile X Messenger Ribonucleoprotein (FMRP) influences ribosomal RNA 2'O-methylation patterns during neuronal differentiation. Its absence alters these epitranscriptome marks, potentially impacting neuronal development and protein synthesis in Fragile X Syndrome.

Keywords:
FMRPRibosomal RNAepitranscriptomeribosomesnoRNA

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Area of Science:

  • Molecular Biology
  • Neuroscience
  • Epigenetics

Background:

  • Fragile X Messenger Ribonucleoprotein (FMRP) loss causes Fragile X Syndrome (FXS), an autism spectrum disorder.
  • FMRP regulates mRNA translation crucial for neuronal development and synaptic plasticity.
  • The precise biochemical mechanism of FMRP's translational regulation remains unclear.

Purpose of the Study:

  • To investigate FMRP's role in modulating ribosomal RNA (rRNA) 2'-O-methylation during neuronal differentiation.
  • To understand how FMRP-mediated rRNA epitranscriptome changes impact neuronal development and protein synthesis.

Main Methods:

  • Studied FMRP interactions with C/D box snoRNAs in H9 ESCs.
  • Analyzed rRNA 2'-O-methylation patterns during ESC differentiation to neuronal precursors and cortical neurons.
  • Assessed global protein synthesis changes across differentiation stages.

Main Results:

  • FMRP interacts with specific C/D box snoRNAs, influencing rRNA 2'-O-methylation patterns in ESCs.
  • rRNA 2'-O-methylation levels decrease progressively during neuronal differentiation.
  • This stepwise methylation change is altered in FMRP-deficient cells, affecting protein synthesis.

Conclusions:

  • FMRP modulates rRNA 2'-O-methylation, a key epitranscriptome modification, during neuronal differentiation.
  • Altered rRNA methylation patterns due to FMRP deficiency may contribute to FXS pathophysiology.
  • Understanding these mechanisms offers insights into neuronal development and FXS treatment strategies.