Saturday, January 8, 2011
Viral nature of the mitochondrial RNA polymerase
Mitochondria contain their own genome, and they transcribe it. Since mitochondria are of bacterial origin, one would expect that their polymerase would be similar to that of bacteria. And it is so the case for chloroplasts, which are also of bacterial origin.
However, mitochondrial polymerase not homologous to that of bacteria, or, for that matter, to cytosolic eukariotic polymerases. It is homologous to... polymerases of T phages, T3 and T7!
However, it is slightly modified. It has an extension at the N-terminus, and this extension is highly variable. Using this extension yeast mitochondrial polymerase interacts with protein Nam1p, which is involved in mRNA stabilization. Nam1p in turn interacts with the whole bunch of mitochondrial membrane proteins which organise translation and following assembly of the proteins constituting the core of cytochrome c oxidase complex (COX).
In this way all the steps of COX formation are connected in the mitochondria: polimerase binds to Nam1p, Nam1p binds to membrane-bound translational enhancers, enhancers bind mRNA and the ribosome, the ribosome itself binds to membrane, and translated protein is inserted in the membrane. There is even a special term for this sort of coupled transcription, translation and insertion - transertion. Very neat system!
Amazingly, different eukaryotes reinvent this system in different ways. Most of the components are clade-specific, and since the system is so very interconnected, it is is very, very different in different eucaryotes. Therefore when yeast geneticists say that they are studying Saccharomyces cerevisiae as a model system in order to understand human mitochondrial translation they are... well... how should I say it? well, they are being over-optimistic.
PS: and phages and mitochondria are trading polymerases both ways! A cyanophage was discovered that has an ex-mitochondrial DNA (not RNA) polymerase!
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Rodeheffer MS, Boone BE, Bryan AC, & Shadel GS (2001). Nam1p, a protein involved in RNA processing and translation, is coupled to transcription through an interaction with yeast mitochondrial RNA polymerase. The Journal of biological chemistry, 276 (11), 8616-22 PMID: 11118450
Naithani S, Saracco SA, Butler CA, & Fox TD (2003). Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae. Molecular biology of the cell, 14 (1), 324-33 PMID: 12529447
Gagliardi D, Stepien PP, Temperley RJ, Lightowlers RN, & Chrzanowska-Lightowlers ZM (2004). Messenger RNA stability in mitochondria: different means to an end. Trends in genetics : TIG, 20 (6), 260-7 PMID: 15145579
Yi-Wah Chan, Remus Mohr, Andrew D. Millard, Antony B. Holmes, Anthony W. Larkum, Anna L. Whitworth, Nicholas H. Mann, David J. Scanlan, Wolfgang R. Hess and Martha R. J. Clokie. Discovery of cyanophage genomes which contain mitochondrial DNA polymerase. Mol Biol Evol (2011) doi: 10.1093/molbev/msr041