Dumas S, Le Hir H, Bodeau-Péan S, Hirsch E, Thermes C, Mallet J
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Paris, France.
J Neurochem. 1996 Jul;67(1):19-25. doi: 10.1046/j.1471-4159.1996.67010019.x.
Alternative splicing of human tyrosine hydroxylase (TH) pre-mRNA produces four mRNAs leading to four different TH isoforms and is thought to have important regulatory functions. We show that the diversity of TH mRNAs is greater than previously described in the autonomous nervous system: New splice junctions corresponding to the skipping of exon 3 were identified by amplification of cDNA synthesized from pheochromocytoma RNA. In all cases the reading frame was maintained. These species were assayed by RNase protection experiments; their abundance (4-6%) was comparable to that of the previously identified human TH-3 and -4 species in normal adrenal medulla. However, higher levels (11-34%) of these species were found in adrenal medullas of patients suffering from progressive supranuclear palsy. Whether such changes are specific to the disease or the consequences of the stress associated with this severe neurodegeneration remains to be established.
人酪氨酸羟化酶（TH）前体mRNA的可变剪接产生四种mRNA，导致四种不同的TH异构体，被认为具有重要的调节功能。我们发现，TH mRNA的多样性比自主神经系统中先前描述的更大：通过扩增从嗜铬细胞瘤RNA合成的cDNA，鉴定出对应于外显子3跳跃的新剪接连接。在所有情况下，阅读框均得以保留。通过核糖核酸酶保护实验对这些种类进行了分析；它们的丰度（4-6%）与正常肾上腺髓质中先前鉴定的人TH-3和-4种类相当。然而，在进行性核上性麻痹患者的肾上腺髓质中发现这些种类的水平更高（11-34%）。这种变化是该疾病特有的，还是与这种严重神经退行性变相关的应激的后果，仍有待确定。
