|Budget Amount *help
¥206,960,000 (Direct Cost: ¥159,200,000、Indirect Cost: ¥47,760,000)
Fiscal Year 2013: ¥31,200,000 (Direct Cost: ¥24,000,000、Indirect Cost: ¥7,200,000)
Fiscal Year 2012: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2011: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
Fiscal Year 2010: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
Fiscal Year 2009: ¥56,160,000 (Direct Cost: ¥43,200,000、Indirect Cost: ¥12,960,000)
We have studied the physiological roles of the CCR4-NOT deadenylase complex by generating mouse lines in which each gene encoding individual subunit of the CCR4-NOT complex is disrupted. Mice thus produced were analyzed pathologically and anatomically, and we so far found that those mice were either embryonic lethal or abnormal in tissue development or showed loss of regulation in immune system and/or energy metabolism. We, therefore, assumed that CCR4-NOT deficient mouse lines could be models of human diseases. We also analyzed the molecular mechanisms by which the CCR4-NOT complex recognizes and degrades poly(A) tail of its target mRNAs. We solved the crystal structures of oligo(dA)-interacting enzymatic subunits CNOT6L and CNOT7. We also found the enzymatic subunits can target poly(A) tail of specific mRNA species through their interaction with regulatory subunits such as CNOT1 and CNOT3 that can recognize specific sequences present at 3'UTR regions of particular mRNAs.