Mechanistic insight into CCR4-NOT deadenylase-mediated heart function control and its potential application for therapeutics

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Akita University
• Principal Investigator: Kuba Keiji 秋田大学, 医学(系)研究科(研究院), 教授 (10451915)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: CCR4-NOT / heart failure / deadenylase / CNOT3

Outline of Final Research Achievements

In this study, we analyzed the mechanisms how CCR4-NOT deadenylase regulates mRNA decay and nucleotide metabolism in controlling heart functions. mRNA decay by CCR4-NOT complex was revealed to alter adenine nucleotide levels in the heart. In addition, bulk mRNA poly(A) shortening and alteration of nucleotide levels were sensed by an autophagy molecule, which is crucial for cardiomyocyte survival. Furthermore, CCR4-NOT-mediated adenine nucleotide regulation was also shown to affect energy-sensing signaling pathway. Both pathways are likely important for CCR4-NOT-mediated heart function control. Finally, we conducted chemical compound screening for CCR4-NOT deadenylase inhibitors.

Free Research Field

循環薬理学