Loss of YTHDF2 Alters the Expression of m 6 A-Modified Myzap and Causes Adverse Cardiac Remodeling

How post-transcriptional regulation of gene expression, such as through -methyladenosine (m A) messenger RNA methylation, impacts heart function is not well understood. We found that loss of the m A binding protein YTHDF2 in cardiomyocytes of adult mice drove cardiac dysfunction. By proteomics, we f...

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Published in:JACC. Basic to translational science 2023-09, Vol.8 (9), p.1180
Main Authors: Golubeva, Volha A, Dorn, Lisa E, Gilbert, Christopher J, Rabolli, Charles P, Das, Anindhya Sundar, Wanasinghe, Vishmi S, Veress, Roland, Terentyev, Dmitry, Accornero, Federica
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Language:English
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Summary:How post-transcriptional regulation of gene expression, such as through -methyladenosine (m A) messenger RNA methylation, impacts heart function is not well understood. We found that loss of the m A binding protein YTHDF2 in cardiomyocytes of adult mice drove cardiac dysfunction. By proteomics, we found myocardial zonula adherens protein (MYZAP) within the top up-regulated proteins in knockout cardiomyocytes. We further demonstrated that YTHDF2 binds m A-modified messenger RNA and controls its stability. Cardiac overexpression of MYZAP has been associated with cardiomyopathy. Thus, our findings provide an important new mechanism for the YTHDF2-dependent regulation of this target and therein its novel role in the maintenance of cardiac homeostasis.
ISSN:2452-302X