Meta-Biol

• Pathways

TFB1M transfers methyl groups from S-adenosylmethionine to the 6 position of adenosine residues at nucleotides 936 and 937 in 12S mitochondrial rRNA (McCulloch et al. 2002, Seidel-Rogol et al. 2003, Cotney et al. 2009, Guja et al. 2013). The mitochondrial RNA polymerase POLRMT associates directly with TFB1M and increases its methylase activity (Surovtseva and Shadel 2013). Alleles of TFB1M modify the severity of hearing loss associated with the A1555G mutation in 12S rRNA (Bykhovskaya et al. 2004). The A1555G mutation may cause hypermethylation of 12S rRNA which activates AMP kinase, E2F1, and apoptosis (Cotney et al. 2009, Raimundo et al. 2012), however the reported hypermethylation and deafness phenotype have been questioned (Lee et al. 2015). Disruption of Tfb1m in mice is lethal and causes loss of adenine methylation of the 12S RNA (Metodiev et al. 2009).