YTHDF1 is pivotal for maintenance of cardiac homeostasis.

The YTH-domain family (YTHDF) of RNA binding proteins can control gene expression at the post-transcriptional level by regulating mRNAs with N-methyladenosine (mA) modifications. Despite the established importance of mA in the heart, the cardiac role of specific mA-binding proteins remains unclear. Here, we characterized the function of YTHDF1 in cardiomyocytes using a newly generated cardiac-restricted mouse model.

YTHDF2 governs muscle size through a targeted modulation of proteostasis.

The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-β pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear.

Loss of YTHDF2 Alters the Expression of mA-Modified Myzap and Causes Adverse Cardiac Remodeling.

How post-transcriptional regulation of gene expression, such as through -methyladenosine (mA) messenger RNA methylation, impacts heart function is not well understood. We found that loss of the mA 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.

The mA methyltransferase METTL3 regulates muscle maintenance and growth in mice.

Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome.

Epitranscriptomics in the Heart: a Focus on mA.

Purpose Of Review: Post-transcriptional modifications are key regulators of gene expression that allow the cell to respond to environmental stimuli. The most abundant internal mRNA modification is N6-methyladenosine (mA), which has been shown to be involved in the regulation of RNA splicing, localization, translation, and decay. It has also been implicated in a wide range of diseases, and here, we review recent evidence of mA's involvement in cardiac pathologies and processes.