Reenan R A, Hanrahan C J, Ganetzky B
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington 06030, USA.
Neuron. 2000 Jan;25(1):139-49. doi: 10.1016/s0896-6273(00)80878-8.
The mle(napts) mutation causes temperature-dependent blockade of action potentials resulting from decreased abundance of para-encoded Na+ channels. Although maleless (mle) encodes a double-stranded RNA (dsRNA) helicase, exactly how mle(napts) affects para expression remained uncertain. Here, we show that para transcripts undergo adenosine-to-inosine (A-to-I) RNA editing via a mechanism that apparently requires dsRNA secondary structure formation encompassing the edited exon and the downstream intron. In an mle(napts) background, >80% of para transcripts are aberrant, owing to internal deletions that include the edited exon. We propose that the Mle helicase is required to resolve the dsRNA structure and that failure to do so in an mle(napts) background causes exon skipping because the normal splice donor is occluded. These results explain how mlen(napts) affects Na+ channel expression and provide new insights into the mechanism of RNA editing.
mle(napts)突变导致动作电位的温度依赖性阻断，这是由para编码的Na+通道丰度降低所致。尽管无雄基因（mle）编码一种双链RNA（dsRNA）解旋酶，但mle(napts)究竟如何影响para的表达仍不确定。在此，我们表明para转录本通过一种机制经历腺苷到肌苷（A-to-I）的RNA编辑，该机制显然需要形成包含编辑外显子和下游内含子的dsRNA二级结构。在mle(napts)背景下，超过80%的para转录本是异常的，这是由于包括编辑外显子在内的内部缺失。我们提出，Mle解旋酶是解开dsRNA结构所必需的，而在mle(napts)背景下未能做到这一点会导致外显子跳跃，因为正常的剪接供体被阻断。这些结果解释了mle(napts)如何影响Na+通道表达，并为RNA编辑机制提供了新的见解。
