Apr 4, 2020

The C-terminal tails of the mitochondrial transcription factors Mtf1 and TFB2M are part of an auto-inhibitory mechanism that regulates DNA binding

The Journal of Biological Chemistry
Urmimala BasuSmita S Patel

Abstract

The structurally homologous Mtf1 and TFB2M proteins serve as transcription initiation factors of the mitochondrial RNA polymerases in Saccharomyces cerevisiae and humans, respectively. These transcription factors directly interact with the non-template strand of the transcription bubble to drive promoter melting. Given the key roles of Mtf1 and TFB2M in promoter-specific transcription initiation, it can be expected that the DNA-binding activity of the mitochondrial transcription factors is regulated to prevent DNA binding at inappropriate times. However, little information is available on how mitochondrial DNA transcription is regulated. While studying C-terminal (C-tail) deletion mutants of Mtf1 and TFB2M, here we stumbled upon a finding suggesting that the flexible C-tail region of these factors autoregulates their DNA-binding activity. Quantitative DNA-binding studies with fluorescence anisotropy-based titrations revealed that Mtf1 with an intact C-tail has no affinity for DNA, but that deletion of the C-tail greatly increases Mtf1's DNA-binding affinity. Similar observations were made with TFB2M, although autoinhibition by the C-tail of TFB2M was not as complete as in Mtf1. Analysis of available TFB2M structures disclosed t...Continue Reading

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Citations

Mentioned in this Paper

Carboxy-Terminal Amino Acid
Gene Deletion
Study
Research Study
DNA Binding
Polrmt protein, mouse
Analysis
DNA
Transcription, Genetic
Deletion Mutation

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