@article{oai:oist.repo.nii.ac.jp:00000730,
 author = {Yamaguchi, Tomokazu and Suzuki, Takashi and Sato, Teruki and Takahashi, Akinori and Watanabe, Hiroyuki and Kadowaki, Ayumi and Natsui, Miyuki and Inagaki, Hideaki and Arakawa, Satoko and Nakaoka, Shinji and Koizumi, Yukio and Seki, Shinsuke and Adachi, Shungo and Fukao, Akira and Fujiwara, Toshinobu and Natsume, Tohru and Kimura, Akinori and Komatsu, Masaaki and Shimizu, Shigeomi and Ito, Hiroshi and Suzuki, Yutaka and Penninger, Josef M. and Yamamoto, Tadashi and Imai, Yumiko and Kuba, Keiji},
 issue = {516},
 journal = {Science Signaling},
 month = {Feb},
 note = {Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In Cnot3-depleted hearts, Atg7 expression was posttranscriptionally increased. Genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice. We further showed that in Cnot3-depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis.},
 title = {The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function},
 volume = {11},
 year = {2018}
}