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

0576970 - BFÚ 2024 RIV CZ eng J - Journal Article
Krejčí, Jana - Arcidiacono, Orazio Angelo - Čegan, Radim - Radaszkiewicz, K. A. - Pacherník, J. - Pirk, J. - Pešl, M. - Fila, P. - Bártová, Eva
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.
Physiological Research. Roč. 72, č. 4 (2023), s. 425-444. ISSN 0862-8408. E-ISSN 1802-9973
Institutional support: RVO:68081707
Keywords : mES cells * hES cells * fto * alkbh5 * Epigenetics * Differentiation * Aging
OECD category: Biochemistry and molecular biology
Impact factor: 2.1, year: 2022
Method of publishing: Open access

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.
Permanent Link: https://hdl.handle.net/11104/0349142