Developmental dynamics of mitochondrial mRNA abundance and editing reveal roles for temperature and the differentiation-repressive kinase RDK1 in cytochrome oxidase subunit II mRNA editing.
Developmental dynamics of mitochondrial mRNA abundance and editing reveal roles for temperature and the differentiation-repressive kinase RDK1 in cytochrome oxidase subunit II mRNA editing.
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布氏锥虫线粒体尿苷插入/缺失编辑的发育调控对于调节寄生虫代谢是必要的，因为它从依赖于哺乳动物血流形式（BSF）中的ATP产生的糖酵解转变为昆虫原环形式（PCF）中的氧化磷酸化。然而，调控mRNA编辑的时机和刺激的特征很差。在这里，我们使用了一个多形T。布氏菌株和定量RT-PCR和液滴数字PCR分析，以评估随着寄生虫从细长BSF逐渐分化为PCF，总mRNA丰度和编辑的变化，并研究个体刺激对线粒体基因表达的影响。我们观察到在细长到粗短的BSF过渡期间几乎没有变化。相反，我们发现，主要是线粒体细胞色素（COI，COII，COIII，和CYb）的mRNA上调后24小时内stumpy BSF刺激分化为PCF在体外和体内采采蝇感染。温度从37°C降低到27°C是增加COII和COIII mRNA和COIV蛋白表达的编辑的关键因素，但不是CYb mRNA或RISP蛋白表达的编辑。我们进一步证明了分化抑制激酶RDK 1的耗尽与温度降低相结合以刺激COII mRNA编辑，并且辅助因子p22是COII mRNA编辑的冷响应上调所需的。总体而言，我们表明，细胞色素mRNA的调节在发展过程中通过不同的刺激，通过各种方法，以增加其丰度和/或编辑。 布氏锥虫是一种单细胞寄生虫，可引起非洲昏睡病和牲畜长角病。该寄生虫具有复杂的生命周期，在人类和采采蝇昆虫载体中由几种发育形式组成。哺乳动物和昆虫宿主提供不同的营养环境，因此T.布鲁氏菌必须调整其新陈代谢，以促进其生存并完成其生命周期。作为T.当布鲁氏菌从人类宿主传播到苍蝇时，寄生虫必须通过称为尿苷插入/缺失编辑的过程来调节其线粒体基因表达，以获得能够被翻译成昆虫宿主中能量产生所需的功能性呼吸链蛋白的mRNA。因此，了解T.布氏杆菌在从哺乳动物宿主到昆虫载体的传递过程中调节线粒体基因表达。
Developmental regulation of mitochondrial uridine insertion/deletion editing in Trypanosoma brucei is necessary to modulate parasite metabolism as it shifts from dependence on glycolysis for ATP production in the mammalian bloodstream form (BSF) to oxidative phosphorylation in the insect procyclic form (PCF). However, the timing and stimuli that regulate mRNA editing have been poorly characterized. Here, we utilized a pleomorphic T. brucei strain and quantitative RT-PCR and droplet digital PCR analyses to evaluate the changes in total mRNA abundance and editing as parasites progressively differentiate from slender BSF to PCF and investigate the effect of individual stimuli on mitochondrial gene expression. We observed little change during the slender-to-stumpy BSF transition. Rather, we found that mainly the mitochondrial cytochrome (COI, COII, COIII, and CYb) mRNAs are upregulated within 24 h after stumpy BSF is stimulated to differentiate to PCF in vitro and during in vivo tsetse fly infections. Temperature reduction from 37°C to 27°C is a critical factor for increasing the editing of COII and COIII mRNAs and COIV protein expression but not the editing of CYb mRNA or RISP protein expression. We further demonstrate that the depletion of the differentiation-repressive kinase RDK1 couples with temperature reduction to stimulate COII mRNA editing, and the accessory factor p22 is required for the cold-responsive upregulation of COII mRNA editing. Overall, we show that cytochrome mRNAs are regulated during development by distinct stimuli through a variety of methods to increase their abundance and/or editing. Trypanosoma brucei is the unicellular parasite that causes African sleeping sickness and nagana disease in livestock. The parasite has a complex life cycle consisting of several developmental forms in the human and tsetse fly insect vector. Both the mammalian and insect hosts provide different nutritional environments, so T. brucei must adapt its metabolism to promote its survival and to complete its life cycle. As T. brucei is transmitted from the human host to the fly, the parasite must regulate its mitochondrial gene expression through a process called uridine insertion/deletion editing to achieve mRNAs capable of being translated into functional respiratory chain proteins required for energy production in the insect host. Therefore, it is essential to understand the mechanisms by which T. brucei regulates mitochondrial gene expression during transmission from the mammalian host to the insect vector.
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影响因子：
3.2
作者：
Desquesnes M;Gonzatti M;Sazmand A;Thévenon S;Bossard G;Boulangé A;Gimonneau G;Truc P;Herder S;Ravel S;Sereno D;Jamonneau V;Jittapalapong S;Jacquiet P;Solano P;Berthier D
通讯作者：
Berthier D
影响因子：
4.5
作者：
Hashimi, Hassan;Cicova, Zdenka;Lukes, Julius
通讯作者：
Lukes, Julius
影响因子：
5.6
作者：
Golden, Daniel E.;Hajduk, Stephen L.
通讯作者：
Hajduk, Stephen L.
影响因子：
1.5
作者：
Burkard, Gabriela;Fragoso, Cristina M.;Roditi, Isabel
通讯作者：
Roditi, Isabel
DOI：
10.1073/pnas.82.10.3380
发表时间：
1985-01-01
影响因子：
11.1
作者：
FEAGIN, JE;STUART, K
通讯作者：
STUART, K