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Updated: Jul 22, 2025

DNAzyme-dependent Analysis of rRNA 2’-O-Methylation
Published on: September 16, 2019
Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions
Sophia J Häfner1, Martin D Jansson1, Kübra Altinel1
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Abstract:
Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2'-O-methylation (2'-O-me) of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here, we examine changes in rRNA 2'-O-me during mouse brain development and tri-lineage differentiation of human embryonic stem cells (hESCs). We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site impacting neuronal differentiation. Modulation of its methylation levels affects ribosome association of the fragile X mental retardation protein (FMRP) and is accompanied by an altered translation of WNT pathway-related mRNAs. Together, these data identify ribosome heterogeneity through rRNA 2'-O-me during early development and differentiation and suggest a direct role for ribosomes in regulating translation during cell fate acquisition.
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