Developmental regulation of edited CYb and COIII mitochondrial mRNAs is achieved by distinct mechanisms in Trypanosoma brucei.
Developmental regulation of edited CYb and COIII mitochondrial mRNAs is achieved by distinct mechanisms in Trypanosoma brucei.
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布氏锥虫中编辑的 CYb 和 COIII 线粒体 mRNA 的发育调节是通过不同的机制实现的。
DOI：
10.1093/nar/gkaa641
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发表时间：
2020
影响因子：
14.9
通讯作者：
Read,LaurieK
中科院分区：
文献类型：
--
作者：
SmithJr,JosephT;Doleželová,Eva;Tylec,Brianna;Bard,JonathanE;Chen,Runpu;Sun,Yijun;Zíková,Alena;Read,LaurieK
布氏锥虫是一种寄生性原生动物，它经历了一个复杂的生命周期，涉及昆虫和哺乳动物宿主，呈现出显着不同的营养环境。线粒体代谢和基因表达受到高度调节，以适应这些环境变化，包括调节需要广泛的尿苷插入/缺失（U-indel）编辑才能成熟的mRNA。在这里，我们使用高通量测序和一种促进生命周期变化的方法来评估发育调控的编辑mRNA表达的机制和时间。我们发现，编辑CYb mRNA在哺乳动物血流形式（BSF）中在编辑起始和/或编辑mRNA稳定性水平下调。相比之下，编辑后的COIII mRNA通过抑制编辑进展而在BSF中被耗尽。我们确定了废除COIII mRNA编辑机制的细胞系特异性差异，包括可能利用终止子gRNA阻止3′至5′编辑进程。通过检查线粒体mRNA水平改变的发育时间，我们还揭示了上鞭毛虫（EMF）、亚循环（MCF）和BSF中转录特异性的发育检查点。这些研究代表了对T过程中编辑的mRNA水平的机制的首次分析。bruceidevelopment和第一个询问EMF和MCF生命周期阶段中的U-indel编辑。
Trypanosoma bruceiis a parasitic protozoan that undergoes a complex life cycle involving insect and mammalian hosts that present dramatically different nutritional environments. Mitochondrial metabolism and gene expression are highly regulated to accommodate these environmental changes, including regulation of mRNAs that require extensive uridine insertion/deletion (U-indel) editing for their maturation. Here, we use high throughput sequencing and a method for promoting life cycle changesin vitroto assess the mechanisms and timing of developmentally regulated edited mRNA expression. We show that edited CYb mRNA is downregulated in mammalian bloodstream forms (BSF) at the level of editing initiation and/or edited mRNA stability. In contrast, edited COIII mRNAs are depleted in BSF by inhibition of editing progression. We identify cell line-specific differences in the mechanisms abrogating COIII mRNA editing, including the possible utilization of terminator gRNAs that preclude the 3′ to 5′ progression of editing. By examining the developmental timing of altered mitochondrial mRNA levels, we also reveal transcript-specific developmental checkpoints in epimastigote (EMF), metacyclic (MCF), and BSF. These studies represent the first analysis of the mechanisms governing edited mRNA levels duringT. bruceidevelopment and the first to interrogate U-indel editing in EMF and MCF life cycle stages.