Southard J N, Barrett B A, Bikbulatova L, Ilkbahar Y, Wu K, Talamantes F
Department of Biology, University of California, Santa Cruz 95064, USA.
Endocrinology. 1995 Jul;136(7):2913-21. doi: 10.1210/endo.136.7.7789316.
Two 5'-untranslated regions (5'UTRs) with distinctly different sequences, designated 5'UTR L1 and 5'UTR L2, were obtained by amplification of complementary DNA from mouse liver and placenta with primers complementary to sequences from the hormone-binding domain common to GH receptor (GHR) and GH-binding protein (GHBP) messenger RNAs (mRNAs). The presence of an open reading frame in the 5'UTR L2 and the high GC content of this sequence suggest that mRNAs containing this 5'UTR may be translated with a lower efficiency than those containing 5'UTR L1. Expression studies showed that 5'UTR L1 and 5'UTR L2 are present in GHR and GHBP mRNAs in both tissues. However, the relative expression of the two 5'UTRs differs between liver and placenta and in liver from different physiological states. The different expression patterns of the L1 and L2 5'UTRs predict that the corresponding 5'-noncoding exons of the GHR/GHBP gene are associated with different regulatory elements. The expression patterns of the 5'UTRs also indicate that there is a linkage between the 5'UTR present in GHR/GHBP gene transcripts and the alternative splicing of these transcripts to yield either GHR or GHBP mRNAs. The 5'-noncoding exon used for transcription of the GHR/GHBP gene, therefore, may be involved in regulating both the ratio of GHR to GHBP transcripts and the efficiency of translation of these transcripts. Transcription from the different 5'-noncoding exons of the GHR/GHBP gene thus may be a critical element in the regulation of the expression of GHR and GHBP and thereby in the control of the responses of different tissues to GH.
通过使用与生长激素受体(GHR)和生长激素结合蛋白(GHBP)信使核糖核酸(mRNA)共有的激素结合域序列互补的引物,从小鼠肝脏和胎盘中扩增互补DNA,获得了两个序列明显不同的5'非翻译区(5'UTR),分别命名为5'UTR L1和5'UTR L2。5'UTR L2中存在开放阅读框以及该序列的高GC含量表明,含有此5'UTR的mRNA的翻译效率可能低于含有5'UTR L1的mRNA。表达研究表明,5'UTR L1和5'UTR L2存在于两种组织的GHR和GHBP mRNA中。然而,这两个5'UTR的相对表达在肝脏和胎盘之间以及不同生理状态的肝脏中有所不同。L1和L2 5'UTR的不同表达模式预示着GHR/GHBP基因相应的5'非编码外显子与不同的调控元件相关。5'UTR的表达模式还表明,GHR/GHBP基因转录本中存在的5'UTR与这些转录本选择性剪接产生GHR或GHBP mRNA之间存在联系。因此,用于GHR/GHBP基因转录的5'非编码外显子可能参与调节GHR与GHBP转录本的比例以及这些转录本的翻译效率。因此,GHR/GHBP基因不同5'非编码外显子的转录可能是调节GHR和GHBP表达从而控制不同组织对GH反应的关键因素。