The fatty acid synthase gene in avian liver. Two mRNAs are expressed and regulated in parallel by feeding, primarily at the level of transcription.

Abstract The rates of synthesis of fatty acid synthase and the levels of its mRNA are high in livers of chicks, ducklings, or goslings fed high-carbohydrate mash diets and low in livers of starved birds, indicating pretranslational regulation of fatty acid synthase activity. Determination of the step(s) at which the nutritional state regulates the fatty acid synthase mRNA level was the objective of this study. Total RNA extracted from gosling or duckling liver contains two discrete fatty acid synthase transcripts, one of about 12,200 nucleotides and the other about 10,800 nucleotides. Both mRNAs are transcribed from the same gene because there is only one fatty acid synthase gene/haploid genome. A combination of 1) comparison of restriction fragment lengths in genomic DNA and cloned fatty acid synthase cDNAs, 2) differential hybridization of cloned cDNAs to the two mRNAs, and 3) sequence analysis indicates that the longer mRNA is a 3'-extension of the shorter one. The half-lives for fatty acid synthase mRNAs in fed ducklings and in starved ducklings were estimated from the rate at which mRNA level approached steady state during starvation or refeeding. The amount of fatty acid synthase mRNA in total liver RNA increased rapidly when starved ducklings were fed a high-carbohydrate mash diet, reaching an apparent steady state of 10 times the initial level after 9 h. The kinetics of accumulation suggested a half-life of 4-6 h for fatty acid synthase mRNA in fed ducklings. When fed ducklings were starved, fatty acid synthase mRNA decayed with a half-life of about 3 h. Therefore, the half-life for fatty acid synthase mRNA appeared to be little affected by feeding or starvation. The levels of both mRNAs changed in parallel indicating that half-lives of the two mRNAs were not regulated differentially. Transcription of the fatty acid synthase gene, as measured in isolated nuclei, increased about 10-fold when starved ducklings were refed for 24-30 h. Most of the increase in transcription occurred within 45 min after feeding was initiated. However, when fed ducklings were starved, the initial decrease in fatty acid synthase mRNA level occurred more rapidly than the decrease in transcription of the fatty acid synthase gene, indicating some degree of post-transcriptional regulation. Nevertheless, after 48 h of starvation, both mRNA level and transcription were decreased to the same extent. Nutritional state, therefore, regulates the transcription of two fatty acid synthase mRNAs from a unique gene. In addition, transient regulation occurs at an as yet undefined post-transcriptional step.