Alternative 5 '-untranslated regions of mouse GH receptor/binding protein messenger RNA are derived from sequences adjacent to the major L2 promoter

Heterogeneity of 5' untranslated region (5'UTR) sequences is a common featu re of growth hormone receptor/ binding protein (GHR/BP) mRNA from a number of species. Two major 5'UTR sequences (designated L1 and L2 in the mouse) h ave been cloned from rodents, ruminants and primates, and are known to corr espond to transcripts generated from independently regulated promoters. A v ariable number of other 5'UTRs with diverse sequences have been cloned fron t rat, human and bovine tissues. To characterize alternative 5'UTR usage in mouse GHR/BP mRNA, we carried out 5' rapid amplification of cDNA ends usin g RNA from non-pregnant mouse liver and adipose tissue. Three novel 5'UTR s equences were obtained. Sequencing of genomic DNA revealed that exons corre sponding to these three sequences are clustered within 1 kb downstream of t he exon encoding 5'UTR L2, and the associated L2 promoter. The novel 5'UTRs are present at very low levels relative to the total pool of GHR/BP mRNA i n liver, fat, kidney, and mammary gland as determined by ribonuclease prote ction assays. On the basis of these data, we propose that these 5'UTR seque nces may result from the use of cryptic transcription start sites and splic e donor sites under the influence of the adjacent L2 promoter/enhancer regi on.