The Distinct Function and Localization of METTL3/METTL14 and METTL16 Enzymes in Cardiomyocytes

0537440 - BFÚ 2021 RIV CH eng J - Článek v odborném periodiku
Arcidiacono, Orazio Angelo - Krejčí, Jana - Bártová, Eva
The Distinct Function and Localization of METTL3/METTL14 and METTL16 Enzymes in Cardiomyocytes.
International Journal of Molecular Sciences. Roč. 21, č. 21 (2020), č. článku 8139. E-ISSN 1422-0067
Grant CEP: GA ČR(CZ) GA18-07384S
Institucionální podpora: RVO:68081707
Klíčová slova: messenger-rna methylation * embryonic stem-cells * cardiac-hypertrophy * gene-expression * m(6)a methyltransferase * histone deacetylase-1 * hdac inhibitors * tet proteins
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
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It has become evident that epitranscriptome events, mediated by specific enzymes, regulate gene expression and, subsequently, cell differentiation processes. We show that methyltransferase-like proteins METTL3/METTL14 and N-6-adenosine methylation (m6A) in RNAs are homogeneously distributed in embryonic hearts, and histone deacetylase (HDAC) inhibitors valproic acid and Trichostatin A (TSA) up-regulate METTL3/METTL14 proteins. The levels of METTL3 in mouse adult hearts, isolated from male and female animals, were lower in the aorta and pulmonary trunks when compared with atria, but METT14 was up-regulated in the aorta and pulmonary trunk, in comparison with ventriculi. Aging caused METTL3 down-regulation in aorta and atria in male animals. Western blot analysis in differentiated mouse embryonic stem cells (mESCs), containing 10-30 percent of cardiomyocytes, showed METTL3/METTL14 down-regulation, while the differentiation-induced increased level of METTL16 was observed in both wild type (wt) and HDAC1 depleted (dn) cells. In parallel, experimental differentiation in especially HDAC1 wild type cells was accompanied by depletion of m6A in RNA. Immunofluorescence analysis of individual cells revealed the highest density of METTL3/METTL14 in alpha-actinin positive cardiomyocytes when compared with the other cells in the culture undergoing differentiation. In both wt and HDAC1 dn cells, the amount of METTL16 was also up-regulated in cardiomyocytes when compared to co-cultivated cells. Together, we showed that distinct anatomical regions of the mouse adult hearts are characterized by different levels of METTL3 and METTL14 proteins, which are changed during aging. Experimental cell differentiation was also accompanied by changes in METTL-like proteins and m6A in RNA, in particular, levels and distribution patterns of METTL3/METTL14 proteins were different from the same parameters studied in the case of the METTL16 protein.
Trvalý link: http://hdl.handle.net/11104/0315165