Tosic M, Roach A, de Rivaz J C, Dolivo M, Matthieu J M
Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
EMBO J. 1990 Feb;9(2):401-6. doi: 10.1002/j.1460-2075.1990.tb08124.x.
Myelin deficient mice (mld) are characterized by tandem duplication of the gene coding for myelin basic protein (MBP). The upstream gene contains a large inversion of the 3' region which includes exons 3-7, and therefore it cannot give rise to mature mRNA and functional protein. MBP and MBP mRNA concentrations in mld brains constitute only approximately 2% of the concentrations present in normal mice. The overall transcription rate of the Mbp gene is normal. In order to explain the discrepancy between mRNA concentration and transcription rate, we studied transcription of each individual gene. The two genes were transcribed independently, although some uninterrupted transcription could not be excluded. The rate of transcription of the upstream gene was higher than that of the downstream gene. This difference was reflected in the concentration of sense and antisense RNA found in nuclei. Our results indicate that the low concentration of the mature mRNA cannot be caused by transcriptional interference. High concentration of nuclear antisense RNA strongly suggests that post-transcriptional regulation occurs in mld mice through formation of double stranded RNA.
髓磷脂缺陷小鼠（mld）的特征是编码髓磷脂碱性蛋白（MBP）的基因发生串联重复。上游基因的3'区域存在大片段倒位，其中包括外显子3 - 7，因此它无法产生成熟的mRNA和功能性蛋白质。mld小鼠大脑中MBP和MBP mRNA的浓度仅约为正常小鼠中浓度的2%。Mbp基因的总体转录速率正常。为了解释mRNA浓度与转录速率之间的差异，我们研究了每个单独基因的转录情况。这两个基因是独立转录的，尽管不能排除一些不间断的转录。上游基因的转录速率高于下游基因。这种差异反映在细胞核中正义和反义RNA的浓度上。我们的结果表明，成熟mRNA的低浓度不是由转录干扰引起的。核内反义RNA的高浓度强烈表明，mld小鼠通过双链RNA的形成发生转录后调控。
