Europe-Finner G N, Phaneuf S, Cartwright E, Mardon H J, López Bernal A
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, UK.
J Mol Endocrinol. 1997 Feb;18(1):15-25. doi: 10.1677/jme.0.0180015.
We have shown previously that expression of 46 and 54 kDa human myometrial G alpha s protein isoforms is increased during gestation and then subsequently decreased during labour. These proteins appear to be coded for by G alpha s-Small (with a serine residue at position 72) and G alpha s-Large (with a serine residue at position 87) mRNA splice variants respectively. In the study presented here we have used a G alpha s cDNA template to generate [32P]cytidine cRNA riboprobes for use in RNase protection assays, so as to measure total myometrial G alpha s mRNA levels in relation to the pattern of expression of G alpha s mRNA splice variants during pregnancy and labour. We report that total levels of human myometrial G alpha s mRNA remain similar in non-pregnant and pregnant women but are substantially reduced during parturition. Our data also provide strong evidence that alternative splicing of G alpha s precursor mRNA has a primary role in regulating expression of G alpha s protein isoforms during pregnancy and labour. The inclusion of an additional serine codon in G alpha s mRNAs during pregnancy involves a switch in alternative splicing pathways. We speculate that this switch may be due to a change in specificity of splicing factors that are modulated during pregnancy and labour.
我们之前已经表明,46 kDa和54 kDa人子宫肌层Gαs蛋白亚型的表达在妊娠期增加,随后在分娩期下降。这些蛋白质似乎分别由Gαs-小(第72位有一个丝氨酸残基)和Gαs-大(第87位有一个丝氨酸残基)mRNA剪接变体编码。在本文所呈现的研究中,我们使用Gαs cDNA模板生成[32P]胞苷cRNA核糖探针,用于核糖核酸酶保护测定,以便测量子宫肌层总Gαs mRNA水平与妊娠和分娩期间Gαs mRNA剪接变体的表达模式的关系。我们报告,人子宫肌层Gαs mRNA的总水平在未怀孕和怀孕女性中保持相似,但在分娩期间大幅降低。我们的数据还提供了强有力的证据,表明Gαs前体mRNA的可变剪接在妊娠和分娩期间调节Gαs蛋白亚型的表达中起主要作用。妊娠期间Gαs mRNA中额外丝氨酸密码子的包含涉及可变剪接途径的转换。我们推测这种转换可能是由于在妊娠和分娩期间被调节的剪接因子特异性的改变。