A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet.

Citation:
Rossetti G, Ermer JA, Stentenbach M, …….. Rackham O, Filipovska A. A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance. Sci Adv. 2021;7(39).

Keywords:
Enzymes; Gene expression; Insulin; RNA; Genetic variants; Insulin release; Mitochondrial energy; Mitochondrial genes; Mitochondria

Abstract:
Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet.