Taking on a second job

Recent research has identified a protein that is essential for mitochondrial function:

Cellular respiration depends on proteins synthesised outside the mitochondrion and imported into it, and on proteins synthesised inside the mitochondrion from its own DNA. Researchers at Karolinska Institutet have now shown that a specific gene (Tfb1m) in the cell’s nucleus codes for a protein (TFB1M) that is essential to mitochondrial protein synthesis. If TFB1M is missing, mitochondria are unable to produce any proteins at all and cellular respiration cannot take place.

Sounds like a crucial protein. So what is TFB1M?

The transcription of genes from mitochondrial DNA requires a mitochondrial RNA polymerase (see POLRMT, MIM 601778) and a DNA-binding transcription factor (see TFAM, MIM 600438). Transcription factor B1 (TFB1M) is a part of this transcription complex.[supplied by OMIM][1]

So it’s an important transcription factor needed to express all the mitochondrial genes.

Is it a recent innovation or does it extend far back into deep time?

To answer this question, I used the human sequence to query the genomic database of Monosiga brevicollis. And I retrieved a significant hit marked as ‘hypothetical protein.’

>gi|167533147|ref|XP_001748254.1| hypothetical protein [Monosiga brevicollis MX1]

I then used this sequence to query ciliate  genomes, green algae, and trypanosomes. They all possess this protein. In fact, microsporidia, which lack mitochondria, also have this protein.

But what about bacteria? It’s ubiquitous among the eubacteria. Archaea? Yeppers, ubiquitous among them too.

So what’s this crucial mitochondrial transcription factor doing in every cell on the planet? Answer – it’s also a dimethyladenosine transferase. This is an enzyme that adds methyl groups to two adjacent adenosine bases in the rRNA component of ribosomes. In other words, is makes essential modifications in the ribosome.

So what we have here is a moonlighting protein (as discussed in TDM). A quick lit review confirms this:

Human mitochondrial transcription factor B1 (h-mtTFB1) has an unprecedented relationship to RNA methyltransferases. Here, we show that this protein methylates a conserved stem-loop in bacterial 16S rRNA and that the homologous sequence in the human mitochondrial 12S molecule is similarly modified. Thus, h-mtTFB1 appears to be dual-function protein, acting both as a transcription factor and an rRNA-modification enzyme.

Seidel-Rogol BL, McCulloch V, Shadel GS. 2003. Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat Genet.33:23-4.

So how would you design a mitochondrial transcription factor needed to activate the entire mitochondrion long before mitochondria existed? Simple. Couple this function to the structure/sequence of a dimethyladenosine transferase. You can count on this enzyme remaining in the biosphere given its important role in processing ribosomes. When mitochondria and their polymerase eventually emerge, the dimethyladenosine transferase can take on its new job in the new realm of the mitochondria – TFB1M.


2 responses to “Taking on a second job

  1. Michael,

    Are introns in the Archaea protein?

  2. Nope

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