A novel function of the mitochondrial transcription factor Mtf1 in fission yeast; Mtf1 regulates the nuclear transcription of srk1

Abstract

In eukaryotic cells, Mtf1 and its homologues function as mitochondrial transcription factors for the mitochondrial RNA polymerase in the mitochondrion. Here we show that in fission yeast Mtf1 exerts a non-mitochondrial function as a nuclear factor that regulates transcription of srk1, which is a kinase involved in the stress response and cell cycle progression. We first found Mtf1 expression in the nucleus. A ChIP-chip approach identified srk1 as a putative Mtf1 target gene. Over expression of Mtf1 induced transcription of the srk1 gene and Mtf1 deletion led to a reduction in transcription of the srk1 gene in vivo. Mtf1 overexpression causes cell elongation in a srk1 dependent manner. Mtf1 overexpression can cause cytoplasmic accumulation of Cdc25. We also provide biochemical evidence that Mtf1 binds to the upstream sequence of srk1. This is the first evidence that a mitochondrial transcription factor Mtf1 can regulate a nuclear gene. Mtf1 may also have a role in cell cycle progression.

Oxidative stress response pathways: Fission yeast as archetype

“…cmk2), become highly increased after environmental perturbations, including oxidative stress (Chen et al, 2003;Smith et al, 2002). Notably, the expression of srk1 is regulated by the mitochondrial TF Mtf1, which has been previously linked to cell cycle control (Sun et al, 2011).…”

Targeting mitochondrial transcription in fission yeast with ETB, an inhibitor of HSP60, the chaperone that binds to the mitochondrial transcription factor Mtf1

“…Mtf1 has been shown to be a transcription factor in both the mitochondrion and the nucleus (Sun et al. 2010).…”

“…2006). To investigate whether Hsp60 is a possible cellular binding partner for Mtf1, we used an Mtf1‐TAP‐tagged strain in which the mtf1 gene is fused to a tandem protein‐A (TAP) tag on the chromosome (Sun et al. 2010), to pull‐down Mtf1‐binding proteins in cells.…”

“…In this experiment, endogenous expression of mtf1 is controlled by the natural mtf1 promoter. The presence of the fused TAP tag does not affect Mtf1 function (Sun et al. 2010).…”

“…As a mitochondrial transcription factor, Mtf1 regulates mitochondrial transcription; overexpression of Mtf1 induces transcription of mitochondrial genes, and in Mtf1 deletion strains, transcription of the mitochondrial genes is reduced; Mtf1 and Rpo41 together bind the mitochondrial promoters and can transcribe the mitochondrial promoters in vitro. In addition, we have also shown that in fission yeast, Mtf1 exerts a nonmitochondrial function as a nuclear factor that regulates transcription of srk1 , a kinase involved in the stress response and cell cycle progression (Sun et al. 2010; Jiang et al.…”