TEFM (c17orf42) is necessary for transcription of human mtDNA
Here we show that c17orf42, hereafter TEFM (transcription elongation factor of mitochondria), makes a critical contribution to mitochondrial transcription. Inactivation of TEFM in cells by RNA interference results in respiratory incompetence owing to decreased levels of H- and L-strand promoter-dist...
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Oxford University Press
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105396/ |
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pubmed-31053962011-06-01 TEFM (c17orf42) is necessary for transcription of human mtDNA Minczuk, Michal He, Jiuya Duch, Anna M. Ettema, Thijs J. Chlebowski, Aleksander Dzionek, Karol Nijtmans, Leo G. J. Huynen, Martijn A. Holt, Ian J. Molecular Biology Here we show that c17orf42, hereafter TEFM (transcription elongation factor of mitochondria), makes a critical contribution to mitochondrial transcription. Inactivation of TEFM in cells by RNA interference results in respiratory incompetence owing to decreased levels of H- and L-strand promoter-distal mitochondrial transcripts. Affinity purification of TEFM from human mitochondria yielded a complex comprising mitochondrial transcripts, mitochondrial RNA polymerase (POLRMT), pentatricopeptide repeat domain 3 protein (PTCD3), and a putative DEAD-box RNA helicase, DHX30. After RNase treatment only POLRMT remained associated with TEFM, and in human cultured cells TEFM formed foci coincident with newly synthesized mitochondrial RNA. Based on deletion mutants, TEFM interacts with the catalytic region of POLRMT, and in vitro TEFM enhanced POLRMT processivity on ss- and dsDNA templates. TEFM contains two HhH motifs and a Ribonuclease H fold, similar to the nuclear transcription elongation regulator Spt6. These findings lead us to propose that TEFM is a mitochondrial transcription elongation factor. Oxford University Press 2011-05 2011-01-27 /pmc/articles/PMC3105396/ /pubmed/21278163 http://dx.doi.org/10.1093/nar/gkq1224 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Minczuk, Michal He, Jiuya Duch, Anna M. Ettema, Thijs J. Chlebowski, Aleksander Dzionek, Karol Nijtmans, Leo G. J. Huynen, Martijn A. Holt, Ian J. |
| spellingShingle |
Minczuk, Michal He, Jiuya Duch, Anna M. Ettema, Thijs J. Chlebowski, Aleksander Dzionek, Karol Nijtmans, Leo G. J. Huynen, Martijn A. Holt, Ian J. TEFM (c17orf42) is necessary for transcription of human mtDNA |
| author_facet |
Minczuk, Michal He, Jiuya Duch, Anna M. Ettema, Thijs J. Chlebowski, Aleksander Dzionek, Karol Nijtmans, Leo G. J. Huynen, Martijn A. Holt, Ian J. |
| author_sort |
Minczuk, Michal |
| title |
TEFM (c17orf42) is necessary for transcription of human mtDNA |
| title_short |
TEFM (c17orf42) is necessary for transcription of human mtDNA |
| title_full |
TEFM (c17orf42) is necessary for transcription of human mtDNA |
| title_fullStr |
TEFM (c17orf42) is necessary for transcription of human mtDNA |
| title_full_unstemmed |
TEFM (c17orf42) is necessary for transcription of human mtDNA |
| title_sort |
tefm (c17orf42) is necessary for transcription of human mtdna |
| description |
Here we show that c17orf42, hereafter TEFM (transcription elongation factor of mitochondria), makes a critical contribution to mitochondrial transcription. Inactivation of TEFM in cells by RNA interference results in respiratory incompetence owing to decreased levels of H- and L-strand promoter-distal mitochondrial transcripts. Affinity purification of TEFM from human mitochondria yielded a complex comprising mitochondrial transcripts, mitochondrial RNA polymerase (POLRMT), pentatricopeptide repeat domain 3 protein (PTCD3), and a putative DEAD-box RNA helicase, DHX30. After RNase treatment only POLRMT remained associated with TEFM, and in human cultured cells TEFM formed foci coincident with newly synthesized mitochondrial RNA. Based on deletion mutants, TEFM interacts with the catalytic region of POLRMT, and in vitro TEFM enhanced POLRMT processivity on ss- and dsDNA templates. TEFM contains two HhH motifs and a Ribonuclease H fold, similar to the nuclear transcription elongation regulator Spt6. These findings lead us to propose that TEFM is a mitochondrial transcription elongation factor. |
| publisher |
Oxford University Press |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105396/ |
| _version_ |
1611456716683083776 |