New aspects of poly(A) tail shortening of mRNA in controlling heart functions

Cardiovascular diseases are major increasing causes of death in developed countries. Coordinated transcriptional and post-transcriptional regulation of gene expression is crucial to maintain normal heart physiology. Dysregulation of these processes causes and/or accompanies multiple pathologies, such as cardiomyopathy and myocardial infarction. The exonuclease-mediated shortening of the mRNA poly(A) tail, a process called deadenylation, is a key step in regulated mRNA degradation, and deadenylation is mostly executed by the CCR4-NOT complex. CCR4-NOT complex is a multi-subunit protein complex, which controls gene expression in the levels from transcription through mRNA deadenylation and protein ubiquitination. We had previously identified CNOT3, a scaffold subunit of the CCR4-NOT complex, as a conserved regulator of heart function in Drosophila and mouse. Our recent genetic data of conditional Cnot3 knockout mice revealed unexpected association of poly(A) shortening and transcriptional activation, which is reprersented by Atg7 and p53. In this review, we introduce our recent progress in dissecting the mechanisms how poly(A) shortening contributes to controlling heart functions and overview new aspects of poly(A) regulation in maintaining cardiac homeostasis.