Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
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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.; Arendrup, Frederic S.; Tehler, Disa; Krogh, Nicolai; Nielsen, Henrik; Kraushar, Matthew L.; Kirkeby, Agnete; Lund, Anders H.
In: Developmental Cell, Vol. 58, No. 17, 2023, p. 1593-1609.e9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
AU - Häfner, Sophia J.
AU - Jansson, Martin D.
AU - Altinel, Kübra
AU - Andersen, Kasper L.
AU - Abay-Nørgaard, Zehra
AU - Ménard, Patrice
AU - Fontenas, Martin
AU - Sørensen, Daniel M.
AU - Gay, David M.
AU - Arendrup, Frederic S.
AU - Tehler, Disa
AU - Krogh, Nicolai
AU - Nielsen, Henrik
AU - Kraushar, Matthew L.
AU - Kirkeby, Agnete
AU - Lund, Anders H.
N1 - Publisher Copyright: © 2023 Elsevier Inc.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - 2′-O-methylation
KW - brain development
KW - cell fate
KW - development
KW - differentiation
KW - human embryonic stem cells
KW - neurogenesis
KW - ribosome
KW - RNA modifications
KW - translation
KW - translation programs
U2 - 10.1016/j.devcel.2023.06.007
DO - 10.1016/j.devcel.2023.06.007
M3 - Journal article
C2 - 37473757
AN - SCOPUS:85169830600
VL - 58
SP - 1593-1609.e9
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 17
ER -
ID: 367600954