据介绍，人类线粒体基因组编码关键的氧化磷酸化系统蛋白，这对有氧能量转导至关重要。它们是由9个单顺反子和两个双顺反子转录本翻译而来的，其天然结构尚未被探索，这在理解线粒体基因表达方面造成了空白。
研究人员设计了线粒体硫酸二甲酯突变分析测序（mitoDMS-MaPseq）方法，并使用期望最大化（DREEM）聚类来检测RNA折叠系，以揭示野生型（WT）和富含亮氨酸的含五肽重复序列蛋白（LRPPRC）缺陷细胞中的天然线粒体信使RNA（mt-mRNA）结构体。研究结果阐明了LRPPRC作为一种保持酶的作用，有助于维持mt-mRNA的折叠和高效翻译。WT线粒体中的mt-mRNA结构，结合代谢标记，揭示了潜在的mRNA程序化翻译暂停和独特的程序化核糖体移码机制。
总之，这一研究定义了线粒体基因表达调控的关键层。这些mt-mRNA折叠图谱为研究不同生理和病理背景下的mt-mRNA结构提供了参考。
附：英文原文
Title: The human mitochondrial mRNA structurome reveals mechanisms of gene expression
Author: J. Conor Moran, Amir Brivanlou, Michele Brischigliaro, Flavia Fontanesi, Silvi Rouskin, Antoni Barrientos
Issue&Volume: 2024-07-19
Abstract: The human mitochondrial genome encodes crucial oxidative phosphorylation system proteins, pivotal for aerobic energy transduction. They are translated from nine monocistronic and two bicistronic transcripts whose native structures remain unexplored, posing a gap in understanding mitochondrial gene expression. In this work, we devised the mitochondrial dimethyl sulfate mutational profiling with sequencing (mitoDMS-MaPseq) method and applied detection of RNA folding ensembles using expectation-maximization (DREEM) clustering to unravel the native mitochondrial messenger RNA (mt-mRNA) structurome in wild-type (WT) and leucine-rich pentatricopeptide repeat–containing protein (LRPPRC)–deficient cells. Our findings elucidate LRPPRC’s role as a holdase contributing to maintaining mt-mRNA folding and efficient translation. mt-mRNA structural insights in WT mitochondria, coupled with metabolic labeling, unveil potential mRNA-programmed translational pausing and a distinct programmed ribosomal frameshifting mechanism. Our data define a critical layer of mitochondrial gene expression regulation. These mt-mRNA folding maps provide a reference for studying mt-mRNA structures in diverse physiological and pathological contexts.
DOI: adm9238
Source: https://www.science.org/doi/10.1126/science.adm9238