Expression data from the liver of wild-type and Cnot3+/- mice: Fed vs 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. We further provide evidence suggesting that CNOT3, by changing its level in response to feeding conditions, affects the activity of the CCR4-NOT deadenylase against poly(A) tails of specific mRNAs coding for proteins involved in metabolism of carbohydrates and fats.

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Morita M, Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T