TFB1M dimethylates adenosine-936 and adenosine-937 of 12S rRNA yielding 6-dimethyladenosine-936 and 6-dimethyladenosine-937

Stable Identifier
Reaction [transition]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
23804760 Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1

Garcia-Diaz, M, Hambardjieva, E, Guja, KE, Venkataraman, K, Yakubovskaya, E, Shi, H, Karzai, AW, Mejia, E

Nucleic Acids Res. 2013
12496758 Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop

McCulloch, V, Seidel-Rogol, BL, Shadel, GS

Nat Genet 2003
11809803 A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine

McCulloch, V, Seidel-Rogol, BL, Shadel, GS

Mol Cell Biol 2002
22341444 Mitochondrial stress engages E2F1 apoptotic signaling to cause deafness

Raimundo, N, Gilliland, TC, McKay, SE, Guan, MX, Shutt, TE, Santos-Sacchi, J, Hohuan, D, Shadel, GS, Cotney, J, Song, L

Cell 2012
26464487 Overexpression of the mitochondrial methyltransferase TFB1M in the mouse does not impact mitoribosomal methylation status or hearing

Douthwaite, S, Lee, S, Vernaleken, A, Rose, S, Larsson, NG, Becker, L, Hrabě De Angelis, M, Fuchs, H, Klopstock, T, Metodiev, MD, Gailus-Durner, V

Hum. Mol. Genet. 2015
19417006 Elucidation of separate, but collaborative functions of the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 in mitochondrial biogenesis reveals new insight into maternally inherited deafness

McKay, SE, Shadel, GS, Cotney, J

Hum. Mol. Genet. 2009
23303773 Transcription-independent role for human mitochondrial RNA polymerase in mitochondrial ribosome biogenesis

Shadel, GS, Surovtseva, YV

Nucleic Acids Res. 2013
19356719 Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome

Park, CB, Lesko, N, Cámara, Y, Larsson, NG, Gustafsson, CM, Hultenby, K, Shi, Y, Metodiev, MD, Wibom, R

Cell Metab. 2009
15110318 Human mitochondrial transcription factor B1 as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation

Wang, D, Shohat, M, Bykhovskaya, Y, Yang, H, Fischel-Ghodsian, N, Estivill, X, Mengesha, E

Mol. Genet. Metab. 2004
Catalyst Activity

rRNA (adenine-N6,N6-)-dimethyltransferase activity of TFB1M [mitochondrial matrix]

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