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

ABSTRACT: 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. Because the levels of CNOT3 protein were decreased under fasting conditions and increased upon refeeding and because CNOT3 could be a positive regulator of the CCR4-NOT deadenylase, we hypothesized that the levels of CCR4-NOT target mRNAs would be lower in fed mice than in fasted mice. We compared the gene expression profiles of fed and fasted wild-type mice. Microarray analysis revealed that approximately 1,200 mRNA transcripts were down-regulated in the livers of fed mice. Of these mRNAs, 68 corresponded to the genes up-regulated in the livers of Cnot3+/- mice and fasted wild-type mice. A large number of the 68 identified genes encoded proteins involved in metabolism, especially lipid metabolism and growth. The livers were isolated from 8-week-old fed wild-type, fasted wild-type and fasted Cnot3+/- mice (n = 2 for each genotype).

ORGANISM(S): Mus musculus

SUBMITTER: Masahiro Morita 

PROVIDER: E-GEOD-18925 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress