Insecticide resistance mediated by an exon skipping event.
Insecticide resistance mediated by an exon skipping event.
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DOI：
10.1111/mec.13882
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发表时间：
2016-11
影响因子：
4.9
通讯作者：
Bass C
中科院分区：
文献类型：
--
作者：
Berger M;Puinean AM;Randall E;Zimmer CT;Silva WM;Bielza P;Field LM;Hughes D;Mellor I;Hassani-Pak K;Siqueira HA;Williamson MS;Bass C
许多基因通过交替使用外显子来增加编码能力。编码昆虫烟碱乙酰胆碱受体 (nAChR) α6 亚基（生物杀虫剂多杀菌素的靶标）的基因就是其中一个例子，它通过相互排斥的外显子的选择性剪接扩大了蛋白质多样性。在这里，我们发现番茄潜叶蛾 Tuta Absoluta 的多杀菌素抗性与 Taα6 剪接的异常调节有关，导致外显子跳跃介导的新型杀虫剂抗性。对多杀菌素选择和未选择的 T. absoluta 菌株的 α6 亚基 cDNA 进行测序，结果显示所选菌株的所有 Taα6 转录物均不含外显子 3，基因组 DNA 和 mRNA 的比较表明这是外显子跳跃的结果。在生存生物测定中，外显子跳跃与多杀菌素耐药性共分离，并且使用修饰的人 nAChR α7（昆虫 α6 模型）对这种改变进行功能表征，证明外显子 3 对于受体功能和多杀菌素敏感性至关重要。 DNA和RNA测序分析表明，外显子跳跃并不是由内含子或外显子顺式调节元件的遗传改变引起的，而是与外显子3a下游的单个表观遗传修饰以及在选择性剪接调节中具有已知作用的反式作用蛋白表达的定量变化有关。我们的结果表明，在抗性进化过程中可以很容易地利用α6基因通过选择性剪接产生转录多样性的内在能力，并将外显子跳跃识别为赋予杀虫剂抗性的分子改变。
Many genes increase coding capacity by alternate exon usage. The gene encoding the insect nicotinic acetylcholine receptor (nAChR) α6 subunit, target of the bio‐insecticide spinosad, is one example of this and expands protein diversity via alternative splicing of mutually exclusive exons. Here, we show that spinosad resistance in the tomato leaf miner, Tuta absoluta is associated with aberrant regulation of splicing of Taα6 resulting in a novel form of insecticide resistance mediated by exon skipping. Sequencing of the α6 subunit cDNA from spinosad selected and unselected strains of T. absoluta revealed all Taα6 transcripts of the selected strain were devoid of exon 3, with comparison of genomic DNA and mRNA revealing this is a result of exon skipping. Exon skipping cosegregated with spinosad resistance in survival bioassays, and functional characterization of this alteration using modified human nAChR α7, a model of insect α6, demonstrated that exon 3 is essential for receptor function and hence spinosad sensitivity. DNA and RNA sequencing analyses suggested that exon skipping did not result from genetic alterations in intronic or exonic cis‐regulatory elements, but rather was associated with a single epigenetic modification downstream of exon 3a, and quantitative changes in the expression of trans‐acting proteins that have known roles in the regulation of alternative splicing. Our results demonstrate that the intrinsic capacity of the α6 gene to generate transcript diversity via alternative splicing can be readily exploited during the evolution of resistance and identifies exon skipping as a molecular alteration conferring insecticide resistance.
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影响因子：
7.3
作者：
Howard, Jonathan M.;Sanford, Jeremy R.
通讯作者：
Sanford, Jeremy R.
DOI：
10.1073/pnas.0500543102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Ibrahim, EC;Schaal, TD;Maniatis, T
通讯作者：
Maniatis, T
影响因子：
12.3
作者：
Langmead B;Trapnell C;Pop M;Salzberg SL
通讯作者：
Salzberg SL
影响因子：
5.8
作者：
Conesa, A;Götz, S;Robles, M
通讯作者：
Robles, M
DOI：
10.1038/nrm.2015.2
发表时间：
2016-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Dominguez AA;Lim WA;Qi LS
通讯作者：
Qi LS