Disease relevance of MTERF

• Similar to the 3,243 mutation in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), the new mutation site was located in the dihydrouridine loop and embedded in the binding region of mitochondrial transcription termination factor [1].
• In this study, rat mTERF has been expressed in vitro and in Escherichia coli [2].

High impact information on MTERF

• In the present work, addition of mTERF to a HeLa cell mitochondrial lysate-based reaction mixture containing an artificial rDNA template did indeed specifically stimulate rDNA transcription [3].
• The human mitochondrial transcription termination factor (mTERF) cDNA has been cloned and expressed in vitro, and two alternative precursors of the protein have been imported into isolated mitochondria and processed to the mature protein [4].
• The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions [4].
• The precursors contain a mitochondrial targeting sequence, and the mature mTERF (342 residues) exhibits three leucine zippers, of which one is bipartite, and two widely spaced basic domains [4].
• The MELAS mutation occurs within the mtDNA binding site for a protein factor (mTERF) that promotes termination of transcription at the 16S rRNA/tRNA(LeuUUR) gene boundary [5].

Biological context of MTERF

• The termination activity has a distinct polarity, and we observed complete transcription termination when the mTERF-binding site is oriented in a forward position relative the heavy strand promoter but only partial transcription termination when the binding site is in the reverse position [6].
• The human mitochondrial transcription termination factor (mTERF) is a 39-kDa protein that terminates transcription at the 3'-end of the 16 S rRNA gene and thereby controls expression of the ribosomal transcription unit of mitochondrial DNA [6].
• The transcription termination activity of human mTERF has been notoriously difficult to study in vitro, and it has been suggested that the activity of the protein is regulated by posttranslational modifications or by protein polymerization [6].
• These data suggest that mTERF functioning in vivo is regulated by phosphorylation [7].
• Here we report that mTERF is the first protein having a role in mammalian mitochondrial gene expression that appears to be controlled by phosphorylation [7].

Anatomical context of MTERF

• When a mitochondrial lysate from HeLa cells was submitted to gel filtration chromatography, mTERF was eluted in two peaks, as detected by immunoblotting [8].

Associations of MTERF with chemical compounds

• No permanganate reactivity was associated with the other regions of the D-loop, including CSB-2 and -3, and with the mTERF contact site [9].
• Dimethyl sulfate footprinting allowed the detection of protein-DNA interactions within the rat analogues of the human binding sites for the transcription termination factor mTERF and for the transcription activating factor mt-TFA [9].

Regulatory relationships of MTERF

• The expression of mTERFL is dramatically inhibited by the addition of serum in serum-starved cells while the mTERF is rather induced [10].

Other interactions of MTERF

• Cloning and functional analysis of human mTERFL encoding a novel mitochondrial transcription termination factor-like protein [10].
• When unphosphorylated, transcription is initiated from the IH2 site and the polymerase reads through the mTERF-dependent termination site, resulting in the transcription of almost the entire H-strand [11].

Analytical, diagnostic and therapeutic context of MTERF

• No mTERF DNA binding activity could be detected in the corresponding gel filtration fractions [8].
• The transcription termination factor (mTERF), which plays a central role in the control of mitochondrial rRNA and mRNA synthesis in mammalian mitochondria, has been previously identified and purified by DNA affinity chromatography from a human mitochondrial lysate (Kruse, B., Narasimhan, N., and Attardi, G. (1989) Cell 58, 391-397) [12].
• To identify novel serum-inhibitory factors and study their roles in cell cycle regulation, we performed mRNA differential display analysis of U251 cells in the presence or absence of serum and cloned a novel gene encoding the human mitochondrial transcription termination factor-like protein (mTERFL) [10].
• Sequence analysis in seven different organisms showed that the protein contains five conserved "mTERF-motifs", three of which include a leucine zipper-like domain [13].

References