TEFM (c17orf42) is necessary for transcription of human mtDNA.

TitleTEFM (c17orf42) is necessary for transcription of human mtDNA.
Publication TypeJournal Article
Year of Publication2011
AuthorsMinczuk, M, He, J, Duch, AM, Ettema, TJ, Chlebowski, A, Dzionek, K, Nijtmans, LGJ, Huynen, MA, Holt, IJ
JournalNucleic Acids Res
Date Published2011 May
KeywordsCatalytic Domain, Cell Line, DNA, Mitochondrial, DNA-Directed RNA Polymerases, Gene Silencing, Humans, Mitochondria, Mitochondrial Proteins, Oxidative Phosphorylation, Protein Structure, Tertiary, RNA, RNA, Mitochondrial, Transcription Factors, Transcriptional Elongation Factors

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.

Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkq1224
PubMed ID21278163
PubMed Central IDPMC3105396
Grant ListBB/F012802/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U105663140 / / Medical Research Council / United Kingdom
MC_U105697135 / / Medical Research Council / United Kingdom