Impact of the POLRMT inhibitor IMT1B on mitochondrial genome copy number in Caenorhabditis elegans

POLRMT is the dedicated mitochondrial RNA polymerase in metazoans and is essential for priming mitochondrial DNA (mtDNA) synthesis. Aberrant POLRMT causes mitochondrial dysfunction and has previously been linked to human metabolic disease. The small molecule IMT1B is an allosteric inhibitor of POLRMT, and its use in diverse model organisms is informative about various aspects of mtDNA synthesis and transcription. Previously, this drug has been shown to be effective in perturbing mtDNA gene expression in human cells and mice. Moreover, a leucine to phenylalanine substitution at position 813 of human POLRMT is predicted to disrupt interaction with the drug. However, the effect of the F813L mutation on the efficacy of POLRMT inhibition (POLRMTi) has not been rigorously tested. Here, we determined by multiple sequence alignment and phylogenetic analysis that this mutation in POLRMT is common among invertebrates, including the model nematode Caenorhabditis elegans. AlphaFold analyses of..., Quantitative PCR; AlphaFold modeling; Phylogenetics, , # Impact of the POLRMT/polrmt-1 inhibitor IMT1B on mitochondrial genome copy number in Caenorhabditis elegans

[https://doi.org/10.5061/dryad.dfn2z35cf](https://doi.org/10.5061/dryad.dfn2z35cf)

**Corresponding investigator:**

Samantha Lewis

\[[[e-mail]](mailto:[e-mail])]

University of California, Berkeley

**Co-Investigators:**

Eve Kakudji, M.S.

University of California, Berkeley

## Description of the data and file structure

This dataset contains raw data, protocols, and analysis used to produce figures and conclusions associated with a poster presented at the American Society of Cell Biology conference in December 2024. 

Multiple sequence alignments are provided as clustalw .aln files that can be opened in MEGA.

Quantitative PCR data is provided as an Excel file.

All other files are in Supplemental Information. Detailed description of the analysis methodology can be found in the Supplemental Information file 'Methods_details_Kakudji.docx'. Inputs to...

线粒体RNA聚合酶（POLRMT）是后生动物中专属的线粒体RNA聚合酶，对线粒体DNA（mtDNA）的合成引物过程至关重要。该酶异常会引发线粒体功能障碍，此前已有研究将其与人类代谢疾病建立关联。小分子化合物IMT1B是POLRMT的变构抑制剂，该药物在多种模式生物中的应用可为mtDNA合成与转录的诸多研究方向提供参考依据。此前已有研究证实，该药物可有效干扰人类细胞与小鼠体内的mtDNA基因表达。
此外，据预测，人类POLRMT第813位氨基酸位点发生亮氨酸至苯丙氨酸的替换后，会破坏其与该药物的相互作用。然而，F813L突变对POLRMT抑制（POLRMTi）效果的影响尚未经过严格验证。
本研究通过多序列比对与系统发育分析，证实POLRMT的该突变在无脊椎动物中普遍存在，其中包括模式线虫秀丽隐杆线虫（Caenorhabditis elegans）。AlphaFold分析、定量PCR（Quantitative PCR）、AlphaFold建模、系统发育学……# POLRMT/polrmt-1抑制剂IMT1B对秀丽隐杆线虫线粒体基因组拷贝数的影响

[https://doi.org/10.5061/dryad.dfn2z35cf](https://doi.org/10.5061/dryad.dfn2z35cf)

**通讯研究者：**
Samantha Lewis
<[e-mail]>
加利福尼亚大学伯克利分校

**共同研究者：**
Eve Kakudji, 理学硕士
加利福尼亚大学伯克利分校

## 数据与文件结构说明
本数据集包含用于生成2024年12月美国细胞生物学会年会海报相关图表与结论的原始数据、实验方案与分析文件。
多序列比对文件采用ClustalW格式的.aln文件，可在MEGA软件中打开。
定量PCR数据以Excel文件格式提供。
其余所有文件均收录于补充材料中。分析方法的详细说明可在补充材料文件"Methods_details_Kakudji.docx"中查阅。本研究的分析输入文件……