Analysis of mitochondrial m1A/G RNA modification reveals links to nuclear genetic variants and associated disease processes

Commun Biol. 2020 Mar 27;3(1):147. doi: 10.1038/s42003-020-0879-3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Dependent Proteases / genetics
  • ATP-Dependent Proteases / metabolism
  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism
  • Databases, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Humans
  • Methylation
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation, Missense
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • RNA Processing, Post-Transcriptional*
  • RNA, Mitochondrial / genetics*
  • RNA, Mitochondrial / metabolism
  • RNA-Seq
  • Ribonuclease P / genetics
  • Ribonuclease P / metabolism
  • tRNA Methyltransferases / genetics
  • tRNA Methyltransferases / metabolism


  • Mitochondrial Proteins
  • RNA, Mitochondrial
  • 1-methyladenosine
  • 1-methylguanine
  • Guanine
  • Trmt61B protein, human
  • tRNA Methyltransferases
  • PRORP protein, human
  • Ribonuclease P
  • ATP-Dependent Proteases
  • LONP1 protein, human
  • Adenosine