Research ArticleCardiovascular Biology

The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function

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Science Signaling  06 Feb 2018:
Vol. 11, Issue 516, eaan3638
DOI: 10.1126/scisignal.aan3638

Protecting the heart by destabilizing mRNA

The removal of polyadenylate tails from mRNAs by the CCR4-NOT complex marks these mRNAs for degradation. Yamaguchi et al. (see also the Focus by Das) found that this activity of this complex was required to prevent cell death in the heart. Mice deficient in a component of this complex suffered from cardiac dysfunction and died of heart failure due to cardiomyocyte death. The CCR4-NOT complex deadenylated Atg7 mRNA, which encodes a protein required for autophagy, a process by which cellular constituents and organelles are digested. The increase in Atg7 in the mutant mice resulted in activation of cell death–associated genes by the transcription factor p53. Drugs that increase autophagy have been explored for the treatment of various diseases, but the authors note that their results raise the possibility of cardiovascular side effects for such drugs.