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POLRMT does not transcribe nuclear genes

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Abstract

Arising from J. E. Kravchenko, I. B. Rogozin, E. V. Koonin & P. M. Chumakov Nature 436, 735–739 (2005); doi:10.1038/nature0384810.1038/nature03848

Mitochondria are involved in a variety of metabolic processes and one of their main functions is to perform oxidative phosphorylation1,2, which requires a crosstalk between the mitochondrial and nuclear genomes to accomplish coordinated gene expression3,4. Splice variants of the mitochondrial RNA polymerase gene (Polrmt) have been reported to encode a nuclear RNA polymerase isoform (spRNAP-IV), which is thought to facilitate this coordination by transcribing a specific subset of nuclear genes5,6,7. Here we report that analysis of Polrmt gene expression, subcellular fractionation and fluorescence microscopy do not support the existence of a nuclear POLRMT isoform in mouse and human cells, and that conditional knockout of Polrmt does not affect expression of the nuclear genes previously reported to be transcribed by spRNAP-IV. We thus conclude that POLRMT has an exclusive mitochondrial role and that it is absolutely required for expression of mitochondrial DNA (mtDNA) in mammalian mitochondria.

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Figure 1: Characterization of POLRMT expression.
Figure 2: Subcellular localization of POLRMT.
Figure 3: Appendix Figure 1 Absence of POLRMT in skeletal muscle does not lead to decreased levels of transcripts from nuclear genes proposed to be transcribed by spRNAP-IV.
Figure 4: Appendix Figure 2 Absence of transcript isoforms that could encode spRNAP-IV in different mouse tissues.
Figure 5: Appendix Figure 3 Absence of the spRNAP-IV protein isoform in different human cell lines.
Figure 6: Appendix Figure 4 Analysis of POLRMT localization in human rho0 cells.
Figure 7: Appendix Figure 5 The human POLRMT antibody detects both POLRMT and spRNAP-IV–Flag in human cells.
Figure 8: Appendix Figure 6 Additional exemplary cells expressing spRNAP-IV–EGFP and non-fused GFP.
Figure 9: Appendix Figure 7 Detection of spRNAP-IV–Flag expressed by transfection of human cells.
Figure 10: Appendix Figure 8 Absence of alternative transcript isoforms encoding spRNAP-IV in human cell lines.
Figure 11: Appendix Figure 9 Comparison of immunofluorescence results obtained after fixation with 4% or 8% formaldehyde.

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Authors and Affiliations

  1. Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany,

    Inge Kühl, Christian Kukat, Benedetta Ruzzenente, Dusanka Milenkovic, Arnaud Mourier, Maria Miranda, Maria Falkenberg & Nils-Göran Larsson

  2. Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden,

    Camilla Koolmeister & Nils-Göran Larsson

  3. Department of Medical Biochemistry and Cell Biology, Göteborgs Universitet, 40530 Göteborg, Sweden,

    Maria Falkenberg

Authors
  1. Inge Kühl
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  2. Christian Kukat
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  3. Benedetta Ruzzenente
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  4. Dusanka Milenkovic
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  5. Arnaud Mourier
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  6. Maria Miranda
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  7. Camilla Koolmeister
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  8. Maria Falkenberg
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  9. Nils-Göran Larsson
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Contributions

C.Ku. did microscopic analysis; B.R., D.M., M.M. and A.M. helped with experimental work and were involved in project planning; C.Ko. performed mouse breedings; M.F. produced the recombinant POLRMT protein used for antibody production; and I.K. performed experimental work, project planning, data analysis and wrote the manuscript together with N.-G.L.

Corresponding author

Correspondence to Nils-Göran Larsson.

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Kühl, I., Kukat, C., Ruzzenente, B. et al. POLRMT does not transcribe nuclear genes. Nature 514, E7–E11 (2014). https://doi.org/10.1038/nature13690

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