INSULIN INCREASES THE PROCESSING EFFICIENCY OF MESSENGER RIBONUCLEIC ACID-S14 NUCLEAR PRECURSOR

Feeding a lipogenic diet increases transcription and enhances processi ng of the rat hepatic messenger RNA (mRNA)-S14 gene. To determine the separate roles of insulin and increased glucose in these processes, we used the streptozotocin-induced diabetic rat model. Diabetes caused a reduction in mature mRNA-S14 in chow- and lipogenic diet-fed animals (P < 0.006 and P < 0.0001, respectively). Insulin restored these level s to normal. Despite the known effects of insulin and carbohydrate on the transcription of this gene, we were unable to demonstrate signific ant changes in the nuclear proteins that bind to carbohydrate response regions. Yet, insulin restored the content of the mRNA by increasing the ratio of mature to precursor mRNA-S14. Insulin significantly incre ased this ratio (P < 0.0001) independent of diet and diabetes, further supporting the action of insulin on increasing processing from precur sor to mature mRNA. The mechanism of the enhanced processing was studi ed by ribonuclease mapping and primer extension analysis. Ribonuclease mapping showed that lipogenic diet feeding increases the efficiency o f processing at a step before formation of the branched form of the pr ecursor mRNA. Taken together, our data demonstrate for the first time that insulin significantly enhances the efficiency of processing of a pre-mRNA.