A common genetic variation of mitochondrial RNA processing enzymes can easily lead to insulin resistance

Insulin resistance and impaired insulin secretion are the main defects of type 2 diabetes

The mitochondrial genome encodes 13 proteins, all of which are an important part of the electron transport chain and adenosine triphosphate (ATP) synthase, responsible for the production of energy through oxidative phosphorylation (OXPHOS)

Mitochondrial RNase P is a protein complex that does not contain catalytic RNA and consists of three proteins: mitochondrial RNase P protein 1 (MRPP1, also known as tRNA methyltransferase 10C homolog, TRMT10C), MRPP2 (HSD17B10, Hydroxysteroid 17-β dehydrogenase 10) and MRPP3 (also known as RNase P catalytic subunit (PRORP))

Mitochondrial ribonuclease P subunit 3 (MRPP3) gene encodes an RNA-binding protein, and a missense variant (rs11156878, Asn437Ser) was recently discovered from it.

According to GWAS predictions, this Asn437Ser mutation, which affects metabolic function and the mitochondrial epitranscriptome, exists at different frequencies in the population.

Researchers used CRISPR-Cas9 technology to knock an equivalent Asn434Ser variant into the mouse Mrpp3 gene to study its effect on metabolism, mitochondrial transcriptome and energy production compared with the wild-type Mrpp3 gene

The accumulation of variation in the human genome is essential to adapt to different nutrient supplies and needs