Jones Andrew K, Buckingham Steven D, Papadaki Magdalini, Yokota Maiko, Sattelle Benedict M, Matsuda Kazuhiko, Sattelle David B
Medical Research Council, Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, United Kingdom.
J Neurosci. 2009 Apr 1;29(13):4287-92. doi: 10.1523/JNEUROSCI.5251-08.2009.
The molecular diversity of many gene products functioning in the nervous system is enhanced by alternative splicing and adenosine-to-inosine editing of pre-mRNA. Using RDL, a Drosophila melanogaster GABA-gated ion channel, we examined the functional impact of RNA editing at several sites along with alternative splicing of more than one exon. We show that alternative splicing and RNA editing have a combined influence on the potency of the neurotransmitter GABA, and the editing isoforms detected in vivo span the entire functional range of potencies seen for all possible edit variants expressed in Xenopus laevis oocytes. The extent of RNA editing is developmentally regulated and can also be linked to the choice of alternative exons. These results provide insights into how the rich diversity of signaling necessary for complex brain function can be achieved by relatively few genes.
通过前体mRNA的可变剪接和腺苷到肌苷的编辑，许多在神经系统中发挥作用的基因产物的分子多样性得到增强。我们使用果蝇的GABA门控离子通道RDL，研究了多个位点的RNA编辑以及多个外显子的可变剪接的功能影响。我们表明，可变剪接和RNA编辑对神经递质GABA的效力有综合影响，并且在体内检测到的编辑异构体涵盖了非洲爪蟾卵母细胞中表达的所有可能编辑变体所观察到的整个效力功能范围。RNA编辑的程度受到发育调控，并且还可以与可变外显子的选择相关联。这些结果为相对较少的基因如何实现复杂脑功能所需的丰富信号多样性提供了见解。
