Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
Heart failure is a leading cause of death in developed countries. The role of mRNA regulation in the pathology of heart failure remains elusive. CCR4-NOT complex is a multi-subunit protein complex constituting exonuclease-mediated shortening of poly(A) tails of mRNA, a process called deadenylation. We had previously elucidated that CNOT3, a scaffold subunit of the CCR4-NOT complex, is a crucial regulator of heart function (Cell 2010, Science Signaling 2018). Here we show our analyses on the multiple roles of CCR4-NOT complex in mouse heart failure models, which is associated with molecular functions of each subunits. While CNOT6L deadenylase subunit regulates gene-specific mRNA regulation of fibrotic genes upon pressure overload stress, global mRNA deadenylation by the whole complex contributes to cardiac energy homeostasis. CNOT4, a temporal interactor of the complex, is protective from several cardiac pathogenic conditions other than pressure overload stress. These results suggest the significance of RNA remodeling in cardiac resilience against various heart stress, and I shall discuss CCR4-NOT-mediated deadenylation/mRNA remodeling and its connection to transcription and translation.
