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Cell Differentiation and Aging Lead To Up-Regulation of FTO, While the ALKBH5 Protein Level Was Stable During Aging but Up-Regulated During in vitro-Induced Cardiomyogenesis

J. Krejčí, OA. Arcidiacono, R. Čegan, K. Radaszkiewicz, J. Pacherník, J. Pirk, M. Pešl, P. Fila, E. Bártová

. 2023 ; 72 (4) : 425-444. [pub] 2023Aug31

Language English Country Czech Republic

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc23018224

FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.

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$a FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.
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$a Arcidiacono, Orazio Angelo $u Department of Cell Biology and Epigenetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
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$a Čegan, Radim $7 xx0309990 $u Department of Cell Biology and Epigenetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
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$a Radaszkiewicz, Katarzyna $7 xx0320047 $u Department of Experimental Biology, Faculty of Sciences, Masaryk University, Brno, Czech Republic
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$a Pacherník, Jiří, $d 1971- $7 xx0088074 $u Department of Experimental Biology, Faculty of Sciences, Masaryk University, Brno, Czech Republic
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$a Pirk, Jan, $d 1948- $7 nlk19990073700 $u IKEM, Cardiovascular Surgery Department, Prague, Czech Republic
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$a Pešl, Martin $7 xx0143722 $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic $u International Clinical Research Center, St. Anne University Hospital, Brno, Czech Republic $u 1st Department of Internal Medicine, Cardioangiology, St. Anne University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Fila, Petr $7 xx0121743 $u Centre of Cardiovascular Surgery and Transplantation, Brno, Czech Republic $u Department of Cardiovascular Surgery and Transplantation, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Bártová, Eva, $d 1968- $7 xx0028314 $u Department of Cell Biology and Epigenetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
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