The kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei.

IF 7.2 1区生物学 Q1 Agricultural and Biological Sciences

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI:10.1371/journal.pbio.3003945

Bianca Manuela Berger, Enrico Santini, Himaja Manjunatha, Lea Trost, Markus Gerber, Hauke S Hillen, Torsten Ochsenreiter

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Abstract

Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP, Tb927.11.5780) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1, Tb927.6.4510) in the Kinetoplastea. The mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein results in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. mTF1 specifically binds to kDNA and since it is unique to the Kinetoplastea, it might prove to be a promising drug target.

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胞浆体特异性转录因子mtTF1对布鲁氏锥虫线粒体基因表达和最大环复制至关重要。

线粒体DNA的复制和基因表达是细胞存活的必要条件。布鲁氏锥虫是一种原生动物和人类寄生虫，线粒体RNA聚合酶（mtRNAP, Tb927.11.5780）在转录和DNA复制中都起作用。本研究鉴定并鉴定了kinetoplstea中的第一个线粒体转录因子（mtTF1, Tb927.6.4510）。mtRNAP和mtTF1形成一种高分子量复合物，定位于着丝体DNA (kDNA)，对寄生虫在两个生命周期阶段的生存至关重要。它们的定位是相互依赖的，两种蛋白质都影响最大环的复制，但不影响小环的复制。敲低任何一种蛋白都会导致基因表达的改变，尤其是影响线粒体基因组的小链。mTF1特异性地与kDNA结合，并且由于它是运动质体所特有的，它可能被证明是一个有希望的药物靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY

CiteScore

15.40

自引率

2.00%

发文量

359

审稿时长

3-8 weeks

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