RNA modifications affect the stability and function of RNA species, regulating important downstream processes. Modification levels are often dynamic, varying between tissues and individuals, although it is not always clear what modulates this or what impact it has on biological systems. Here, we quantify variation in m1A/G RNA modification levels at functionally important positions in the human mitochondrial genome across 11,552 samples from 39 tissue/cell types and find that modification levels are associated with mitochondrial transcript processing. We identify links between mitochondrial RNA modification levels and genetic variants in the nuclear genome, including a missense mutation in LONP1, and find that genetic variants within MRPP3 and TRMT61B are associated with RNA modification levels across a large number of tissues. Genetic variants linked to RNA modification levels are associated with multiple disease/disease-related phenotypes, including blood pressure, breast cancer and psoriasis, suggesting a role for mitochondrial RNA modification in complex disease.

RNA修饰影响RNA种类的稳定性和功能，调节重要的下游过程。修饰水平通常是动态的，在组织和个体之间变化，尽管并不总是清楚是什么对其进行调制或对生物系统产生何种影响。在这里，我们量化了来自39个组织/细胞类型的11,552个样品中人线粒体基因组中功能重要位置的m1A / G RNA修饰水平的变化，并发现修饰水平与线粒体转录本加工相关。我们确定线粒体RNA修饰水平和核基因组中的遗传变异之间的联系，包括LONP1中的错义突变，并发现MRPP3和TRMT61B中的遗传变异与大量组织中的RNA修饰水平相关。与RNA修饰水平相关的遗传变异与多种疾病/疾病相关的表型有关，包括血压，乳腺癌和牛皮癣，表明线粒体RNA修饰在复杂疾病中的作用。