Mar 8, 2020

Auto-inhibitory regulation of DNA binding by the C-terminal tails of the mitochondrial transcription factors Mtf1 and TFB2M

BioRxiv : the Preprint Server for Biology
Urmimala BasuSmita S Patel

Abstract

The structurally homologous Mtf1 and TFB2M proteins serve as transcription initiation factors of the Saccharomyces cerevisiae and human mitochondrial RNA polymerases, 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 is expected that the DNA binding activity of the mitochondrial transcription factors would be regulated to prevent DNA binding at inappropriate times. However, there is little information on how mitochondrial DNA transcription is regulated. While studying the C-tail deletion mutants of Mtf1 and TFB2M, we stumbled upon a new finding that suggested that the flexible C-tail region of these factors autoregulates their DNA binding activity. Quantitative DNA binding studies with fluorescence anisotropy-based titrations show that Mtf1 with an intact C-tail has no affinity for the DNA but the deletion of C-tail greatly increases the DNA binding affinity. Similar observations were made with TFB2M, although autoinhibition by the C-tail of TFB2M was not as absolute as in Mtf1. Analysis of available TFB2M structures show that the C-tail makes intra...Continue Reading

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Mentioned in this Paper

DNA-Binding Proteins
Transcription Initiation
Polrmt protein, mouse
Entire Tail of Helix
TFB2M protein, human
Finding
Mitochondria
DNA Binding
Transcription Factor
Transcription, DNA-dependent

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