Petit Stéphane, Meary Fleur, Pibouin Laurence, Jeanny Jean-Claude, Fernandes Isabelle, Poliard Anne, Hotton Dominique, Berdal Ariane, Babajko Sylvie
INSERM U872, Equipe 5, Laboratoire de Biologie Oro-Faciale et Pathologie, Paris, France.
J Cell Physiol. 2009 Aug;220(2):303-10. doi: 10.1002/jcp.21762.
The Msx1 homeogene plays an important role in epithelial-mesenchymal interactions leading organogenesis. Msx1 gene is submitted to bidirectional transcription generating a long non-coding antisense (AS) RNA potentially involved in Msx1 expression regulation. RT-Q-PCR and RNA-FISH studies indicated that transient overexpression of the Msx1 AS transcript in 705IC5 mouse odontoblasts decreased the abundance of endogenous Msx1 S mRNA at the post-transcriptional level. Conversely, Msx1 overexpression increased the AS RNA level probably by activating AS transcription. In vivo mapping by RT-PCR evidenced both Msx1 RNAs in all adult mouse tissues tested raising the issue of Msx1 function during adulthood. The expression patterns of the two RNAs were similar, confirming the tight S/AS relationship. In particular, both Msx1 mRNAs and Msx1 protein were similarly distributed in eyes, and were found in regions with a common ectodermic origin and in cells potentially involved in regeneration. In conclusion, we report that Msx1 S RNA is negatively controlled by its AS RNA at a post-transcriptional level, and that the AS RNA is retrocontrolled positively by Msx1. The tight link between Msx1 S and AS RNAs constitutes a regulatory loop resulting in a fine-tuned expression of Msx1 which appears to be significant for adult homeostasis.
Msx1同源基因在上皮-间充质相互作用导致器官形成的过程中发挥重要作用。Msx1基因进行双向转录，产生一种可能参与Msx1表达调控的长链非编码反义（AS）RNA。逆转录定量聚合酶链反应（RT-Q-PCR）和RNA荧光原位杂交（RNA-FISH）研究表明，在705IC5小鼠成牙本质细胞中瞬时过表达Msx1反义转录本会在转录后水平降低内源性Msx1 S mRNA的丰度。相反，Msx1过表达可能通过激活反义转录增加AS RNA水平。通过RT-PCR进行的体内定位证明，在所有测试的成年小鼠组织中都存在这两种Msx1 RNA，这就引发了成年期Msx1功能的问题。两种RNA的表达模式相似，证实了S/AS之间的紧密关系。特别是，Msx1 mRNA和Msx1蛋白在眼睛中的分布相似，并且在具有共同外胚层起源的区域以及可能参与再生的细胞中被发现。总之，我们报告Msx1 S RNA在转录后水平受到其AS RNA的负调控（负向控制），而AS RNA受到Msx1的正向反馈调控（正向逆转控制）。Msx1 S RNA和AS RNA之间的紧密联系构成了一个调控环，导致Msx1的表达得到微调，这似乎对成年期的稳态具有重要意义。
