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Transcription of mammalian messenger RNAs by a nuclear RNA polymerase of mitochondrial origin


Transcription of eukaryotic genes is performed by three nuclear RNA polymerases, of which RNA polymerase II is thought to be solely responsible for the synthesis of messenger RNAs1. Here we show that transcription of some mRNAs in humans and rodents is mediated by a previously unknown single-polypeptide nuclear RNA polymerase (spRNAP-IV). spRNAP-IV is expressed from an alternative transcript of the mitochondrial RNA polymerase gene (POLRMT). The spRNAP-IV lacks 262 amino-terminal amino acids of mitochondrial RNA polymerase, including the mitochondrial-targeting signal, and localizes to the nucleus. Transcription by spRNAP-IV is resistant to the RNA polymease II inhibitor α-amanitin but is sensitive to short interfering RNA specific for the POLRMT gene. The promoters for spRNAP-IV differ substantially from those used by RNA polymerase II, do not respond to transcriptional enhancers and contain a common functional sequence motif.

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Figure 1: The POLRMT gene is a source of mitochondrial and nuclear protein products.
Figure 2: Two distinct POLRMT -specific polypeptides are encoded by alternative transcripts.
Figure 3: A nuclear protein product of the POLRMT gene participates in the expression of the ZBTB1 , MGC3265 and ALDH12 genes.
Figure 4: Transcription from the ALDH12 and ZBTB1 promoters depends on spRNAP-IV.

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The work was supported by funds provided by The Lerner Research Institute to P.M.C. and by NIH and RFBR to P.M.C.

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Correspondence to Peter M. Chumakov.

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Supplementary information

Supplementary Figures

Supplementary Figures S1-S10 with legends and additional references. (PDF 1417 kb)

Supplementary Notes

Contains Supplementary Methods, Supplementary Table and information on microarray experiment design in MIAME-copliant format. (PDF 68 kb)

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Kravchenko, J., Rogozin, I., Koonin, E. et al. Transcription of mammalian messenger RNAs by a nuclear RNA polymerase of mitochondrial origin. Nature 436, 735–739 (2005).

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