Expression data from the liver of wild-type and Cnot3+/- mice: Fasted

Decay of mRNAs initiates with shortening of the poly(A) tail. Although the CCR4-NOT complex participates in deadenylation, how it becomes activates remain obscure. We show that complete deficiency in CNOT3, subunit 3 of this complex, is lethal in mice, but that heterozygotes survive as lean mice with hepatic and adipose tissues containing reduced lipid levels. Cnot3+/- mice have enhanced metabolic rates and remain lean on high-fat diets. To examine the underlying mechanisms by which CNOT3 is involved in the control of metabolic balance, we compared the gene expression profiles of wild-type and Cnot3+/- mice using Affymetrix microarray technology. We chose to analyze the liver because the CNOT3 level in the liver was affected by the feeding condition and because the liver plays a major role in glucose and lipid metabolism. The livers were isolated from 12-week-old wild-type and Cnot3+/- mice (n = 2 for each genotype).信使RNA（mRNA）的降解始于多聚腺苷酸尾（poly(A) tail）的缩短。尽管CCR4-NOT复合物参与了脱腺苷酸化过程，但其激活机制仍不明确。本研究发现，该复合物的亚基CNOT3完全缺失会导致小鼠致死，但杂合子小鼠可存活，且体型消瘦，其肝脏和脂肪组织内脂质水平降低。Cnot3+/-小鼠的代谢速率提升，即使在高脂饮食条件下仍能保持消瘦体型。为探究CNOT3参与代谢平衡调控的潜在机制，本研究采用Affymetrix基因芯片技术，对比了野生型与Cnot3+/-小鼠的基因表达谱。本研究选择肝脏作为分析对象，原因在于肝脏内CNOT3的表达水平受进食状态影响，且肝脏在糖脂代谢中发挥核心作用。实验样本取自12周龄的野生型与Cnot3+/-小鼠的肝脏（每种基因型各2只）。