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

Häfner, Sophia J. ; Jansson, Martin D. ; Altinel, Kübra ; Andersen, Kasper L. ; Abay-Nørgaard, Zehra ; Ménard, Patrice ; Fontenas, Martin ; Sørensen, Daniel M. ; Gay, David M. and Arendrup, Frederic S. , et al. (2023) In Developmental Cell 58(17). p.9-1609
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
2′-O-methylation, brain development, cell fate, development, differentiation, human embryonic stem cells, neurogenesis, ribosome, RNA modifications, translation, translation programs
in
Developmental Cell
volume
58
issue
17
pages
9 - 1609
publisher
Cell Press
external identifiers
  • scopus:85169830600
  • pmid:37473757
ISSN
1534-5807
DOI
10.1016/j.devcel.2023.06.007
language
English
LU publication?
yes
id
f0e5ea22-3b9f-4ed1-b5dc-58023cacb24d
date added to LUP
2023-10-23 15:25:49
date last changed
2025-01-26 09:22:20
@article{f0e5ea22-3b9f-4ed1-b5dc-58023cacb24d,
  abstract     = {{<p>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.</p>}},
  author       = {{Häfner, Sophia J. and Jansson, Martin D. and Altinel, Kübra and Andersen, Kasper L. and Abay-Nørgaard, Zehra and Ménard, Patrice and Fontenas, Martin and Sørensen, Daniel M. and Gay, David M. and Arendrup, Frederic S. and Tehler, Disa and Krogh, Nicolai and Nielsen, Henrik and Kraushar, Matthew L. and Kirkeby, Agnete and Lund, Anders H.}},
  issn         = {{1534-5807}},
  keywords     = {{2′-O-methylation; brain development; cell fate; development; differentiation; human embryonic stem cells; neurogenesis; ribosome; RNA modifications; translation; translation programs}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{17}},
  pages        = {{9--1609}},
  publisher    = {{Cell Press}},
  series       = {{Developmental Cell}},
  title        = {{Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions}},
  url          = {{http://dx.doi.org/10.1016/j.devcel.2023.06.007}},
  doi          = {{10.1016/j.devcel.2023.06.007}},
  volume       = {{58}},
  year         = {{2023}},
}