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

KREJCI, Jana, Orazio Angelo ARCIDIACONO, Radim ČEGAN, Katarzyna Anna RADASZKIEWICZ, Jiří PACHERNÍK, Jan PIRK, Martin PEŠL, Petr FILA and Eva BARTOVA. 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. Praha: Fyziologický ústav AV ČR, 2023, vol. 72, No 4, p. 425-444. ISSN 0862-8408. Available from: https://dx.doi.org/10.33549/physiolres.935078.

Basic information

• Original name: 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
• Authors: KREJCI, Jana (203 Czech Republic), Orazio Angelo ARCIDIACONO (380 Italy), Radim ČEGAN (203 Czech Republic), Katarzyna Anna RADASZKIEWICZ (616 Poland, belonging to the institution), Jiří PACHERNÍK (203 Czech Republic, belonging to the institution), Jan PIRK (203 Czech Republic), Martin PEŠL (203 Czech Republic, belonging to the institution), Petr FILA (203 Czech Republic, belonging to the institution) and Eva BARTOVA.
• Edition: Physiological research, Praha, Fyziologický ústav AV ČR, 2023, 0862-8408.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30201 Cardiac and Cardiovascular systems
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.100 in 2022
• RIV identification code: RIV/00216224:14310/23:00132199
• Organization unit: Faculty of Science
• Doi: http://dx.doi.org/10.33549/physiolres.935078
• UT WoS: 001078316100002
• Keywords in English: mES cells; hES cells; FTO; ALKBH5; Epigenetics; Differentiation; Aging
• Tags: 14110115, 14110513, 14110911, podil, rivok
• Tags: International impact, Reviewed

Abstract

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.