The yeast mitochondrial RNA polymerase specificity factor, MTF1, is similar to bacterial sigma factors.

Jang, Sei Heon; Jaehning, Judith A.

doi:10.1016/s0021-9258(18)54622-6

Cited by 144 publications

(13 citation statements)

References 42 publications

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“…These significant differences in promoter recognition between y-and h-mtRNAP ICs suggest that disrupting the -1 to -4 NT DNA binding sites in MTF1 can be a strategy for developing inhibitors to treat yeast infections. The set of interactions between MTF1 and AAGT sequence is reminiscent of the interaction of the sigma 2 region of bacterial sigma factors with the -10 element in bacterial RNAP initiation complexes (Jang and Jaehning, 1991;Lee and Borukhov, 2016;Lin et al, 2017).…”

Section: Interactions Between Y-mtrnap and Mtf1mentioning

confidence: 99%

Cryo-EM Structures Reveal Transcription Initiation Steps by Yeast Mitochondrial RNA Polymerase

et al. 2020

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Mitochondrial RNA polymerase (mtRNAP) is crucial in cellular energy production yet, understanding of mitochondrial DNA transcription initiation lags that of bacterial and nuclear DNA transcription. We report structures of two transcription initiation intermediate states of yeast mtRNAP that explain promoter melting, template alignment, DNA scrunching, abortive synthesis, and transition into elongation. In partially-melted initiation complex (PmIC), transcription factor MTF1 makes base-specific interactions with flipped non-template (NT) -4 to -1 nucleotides 'AAGT' of the DNA promoter. In the initiation complex (IC), the template in the expanded 7-mer bubble positions the RNA and NTP analog, UTP S, while NT scrunches into an NT-loop. The scrunched NT-loop is stabilized by centrally positioned MTF1 C-tail. The IC and PmIC states coexist in solution revealing a dynamic equilibrium between two functional states. Frequent scrunching/unscruching transitions, and the imminent steric clashes of inflating NT-loop and growing RNA:DNA with the C-tail explain abortive synthesis and transition into elongation.

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Section: Interactions Between Y-mtrnap and Mtf1mentioning

confidence: 99%

Cryo-EM Structures Reveal Transcription Initiation Steps by Yeast Mitochondrial RNA Polymerase

et al. 2020

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“…Yeast mtRNA polymerase (Rpo41p) and POLRMT depend on additional factors for specific transcription initiation, and each alone exhibits only nonspecific transcriptional activity. However, the cloning of the yeast specificity factor (Mtf1p or sc-mtTFB) revealed that it was unrelated to h-mtTFA (Jang and Jaehning, 1991). Furthermore, the yeast homolog of h-mtTFA (called Abf2p) lacks the critical C-terminal tail domain and has no direct role in transcription initiation (Xu and Clayton, 1992), fueling speculation that human and yeast mitochondria utilize nonorthologous transcription machinery (i.e., Rpo41p and Mtf1p in yeast and POLRMT and mtTFA in humans).…”

Section: Mitochondrial Transcription Factors B1 and B2mentioning

confidence: 99%

Initiation and Beyond: Multiple Functions of the Human Mitochondrial Transcription Machinery

2006

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Mitochondria contain their own DNA (mtDNA) that is expressed and replicated by nucleus-encoded factors imported into the organelle. Recently, the core human mitochondrial transcription machinery has been defined, comprising a bacteriophage-related mtRNA polymerase (POLRMT), an HMG-box transcription factor (h-mtTFA), and two transcription factors (h-mtTFB1 and h-mtTFB2) that also serve as rRNA methyltransferases. Here, we describe these transcription components as well as recent insights into the mechanism of human mitochondrial transcription initiation and its regulation. We also discuss novel roles for the mitochondrial transcription machinery beyond transcription initiation, including priming of mtDNA replication, packaging of mtDNA, coordination of ribosome biogenesis, and coupling of transcription to translation.

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“…The yeast mtRNAP is a nuclear-encoded two-subunit ''holoenzyme'' consisting of the catalytically active core polymerase, Rpo41 (Kelly et al, 1986), and an accessory factor, Mtf1 (Jang and Jaehning, 1991). Rpo41 and the closely related core mtRNAPs from other eukaryotes are homologous to the T7 bacteriophage family of single-subunit RNAPs (Cermakian et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Mtf1 is an essential component of the yeast mtRNAP, and homologs (mtTFB) have been identified in flies, mice, and humans, where they are required for selective transcription of promoter-containing templates in vitro (Falkenberg et al, 2002;Matsushima et al, 2005;McCulloch et al, 2002;Rantanen et al, 2003). Mtf1 was originally defined as a specificity factor required for promoter utilization (Jang and Jaehning, 1991;Mangus et al, 1994), but recent work has shown that, instead, Mtf1 is important for forming or stabilizing the open promoter during initiation . Therefore, Rpo41, like its phage counterparts, comprises all the necessary contacts for promoter recognition.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Transcription Is Regulated via an ATP “Sensing” Mechanism that Couples RNA Abundance to Respiration

Amiott

Jaehning

2006

Molecular Cell

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The information encoded in both the nuclear and mitochondrial genomes must be coordinately regulated to respond to changes in cellular growth and energy states. Despite identification of the mitochondrial RNA polymerase (mtRNAP) from several organisms, little is known about mitochondrial transcriptional regulation. Studying the shift from fermentation to respiration in Saccharomyces cerevisiae, we have demonstrated a direct correlation between in vivo changes in mitochondrial transcript abundance and in vitro sensitivity of mitochondrial promoters to ATP concentration (K(m)ATP). Consistent with the idea that the mtRNAP itself senses in vivo ATP levels, we found that transcript abundance correlates with respiration, but only when coupled to mitochondrial ATP synthesis. In addition, we characterized mutations in the mitochondrial promoter and the mtRNAP accessory factor Mtf1 that alter both in vitro K(m)ATP and in vivo transcription in response to respiratory changes. We propose that shifting cellular pools of ATP coordinately control nuclear and mitochondrial transcription.

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The yeast mitochondrial RNA polymerase specificity factor, MTF1, is similar to bacterial sigma factors.

Cited by 144 publications

References 42 publications

Cryo-EM Structures Reveal Transcription Initiation Steps by Yeast Mitochondrial RNA Polymerase

Cryo-EM Structures Reveal Transcription Initiation Steps by Yeast Mitochondrial RNA Polymerase

Initiation and Beyond: Multiple Functions of the Human Mitochondrial Transcription Machinery

Mitochondrial Transcription Is Regulated via an ATP “Sensing” Mechanism that Couples RNA Abundance to Respiration

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