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Ribosomal RNA 2’-O-methylation dynamics impact cell fate decisions

SJ Häfner, MD Jansson, K Altinel, ML Kraushar, KL Andersen, Z Caldwell Abay-Nørgaard, M Fontenas, DM Sørensen, DM Gay, FS Arendrup, D Tehler, N Krogh, H Nielsen, A Kirkeby, View ORCID ProfileAH Lund
doi: https://doi.org/10.1101/2022.09.24.509301
SJ Häfner
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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  • For correspondence: sophia.hafner@bric.ku.dk anders.lund@bric.ku.dk
MD Jansson
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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K Altinel
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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ML Kraushar
2Max Planck Institute for Molecular Genetics, Berlin, Germany
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KL Andersen
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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Z Caldwell Abay-Nørgaard
3Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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M Fontenas
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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DM Sørensen
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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DM Gay
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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FS Arendrup
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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D Tehler
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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N Krogh
4Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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H Nielsen
4Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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A Kirkeby
3Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
5Wallenberg Center for Molecular Medicine, Department of Experimental Medical Science, Lund University, Sweden
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AH Lund
1Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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  • ORCID record for AH Lund
  • For correspondence: sophia.hafner@bric.ku.dk anders.lund@bric.ku.dk
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Abstract

Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome itself exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2’-O-methylation of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here we explore changes in rRNA 2’-O-methylation during mouse brain development and during tri-lineage differentiation of human embryonic stem cells. We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site which impacts neuronal differentiation. Modulation of its methylation levels affects ribosome association of the Fragile X Mental Retardation Protein and translation of WNT pathway-related mRNAs. Together, the data reveals ribosome heterogeneity through rRNA 2’-O-methylation during early development and differentiation and suggests a direct role for ribosomes in regulating translation during cell fate acquisition.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 25, 2022.
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Ribosomal RNA 2’-O-methylation dynamics impact cell fate decisions
SJ Häfner, MD Jansson, K Altinel, ML Kraushar, KL Andersen, Z Caldwell Abay-Nørgaard, M Fontenas, DM Sørensen, DM Gay, FS Arendrup, D Tehler, N Krogh, H Nielsen, A Kirkeby, AH Lund
bioRxiv 2022.09.24.509301; doi: https://doi.org/10.1101/2022.09.24.509301
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Ribosomal RNA 2’-O-methylation dynamics impact cell fate decisions
SJ Häfner, MD Jansson, K Altinel, ML Kraushar, KL Andersen, Z Caldwell Abay-Nørgaard, M Fontenas, DM Sørensen, DM Gay, FS Arendrup, D Tehler, N Krogh, H Nielsen, A Kirkeby, AH Lund
bioRxiv 2022.09.24.509301; doi: https://doi.org/10.1101/2022.09.24.509301

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