TFB2M Human

TFB2M was identified through database searches for sequences homologous to the Schizosaccharomyces pombe Mtf1 protein . It encodes a 396-amino acid protein and shares 53% amino acid identity with its mouse homolog . TFB2M is highly homologous to bacterial rRNA dimethyltransferases, suggesting that an RNA-modifying enzyme was recruited during evolution to function as a mitochondrial transcription factor .

The primary function of TFB2M is to support the transcription of mtDNA. It works in conjunction with mitochondrial RNA polymerase (POLRMT) and mitochondrial transcription factor A (TFAM) to initiate transcription from promoter sequences . TFB2M is at least one order of magnitude more active in promoting transcription than TFB1M . This activity is independent of its rRNA methyltransferase activity, which is primarily associated with TFB1M .

TFB2M plays a key role in mitochondrial biogenesis, performing unique yet cooperative functions with TFB1M . While TFB1M is involved in the methylation of mitochondrial 12S rRNA, necessary for normal mitochondrial translation, metabolism, and cell growth, TFB2M is primarily responsible for mtDNA transcription and maintenance .

TFB2M is expressed ubiquitously in human tissues . Its expression is regulated to meet the complex physiological demands of mammalian metabolism. The presence of two proteins (TFB1M and TFB2M) that interact with POLRMT allows for flexible regulation of mtDNA gene expression .

Mutations or dysregulation of TFB2M can lead to mitochondrial dysfunction, which is associated with various human diseases. Understanding the function and regulation of TFB2M is crucial for developing therapeutic interventions for mitochondrial disorders .