High impact information on MTF2

• This connection is mediated in large part by its interactions with the matrix protein Nam1p and, based on genetic phenotypes, the mitochondrial membrane protein Sls1p [1].
• Here we demonstrate by specific labeling of mitochondrial gene products in vivo that Nam1p and Sls1p indeed work together in a pathway that is required globally for efficient mitochondrial translation [1].
• In addition, mutations in the amino-terminal domain result specifically in decreased steady-state levels of mature mitochondrial CYTB and COXI transcripts, which is a primary defect observed in NAM1 null mutant yeast strains [2].
• Phenotypic analysis of deletion and point mutations, in conjunction with a yeast two-hybrid assay, revealed that Nam1p, a protein involved in RNA processing and translation in mitochondria, binds specifically to this domain [2].
• Change of serine309 into proline causes temperature sensitivity of the nuclear NAM1/MTF2 gene product for yeast mitochondria [3].

Biological context of MTF2

• Comparison of the 5' upstream regions of MTF2 and a previously characterized mitochondrial transcription factor (MTF1) revealed common sequence motifs which may be important for coordinated regulation of gene expression [4].
• A fusion plasmid enabling bacterial over-expression of the corresponding protein-A-NAM1 cognate was constructed and subsequently employed as an antigen to raise polyclonal antibodies [5].
• The significance of this interaction in vivo was demonstrated by the fact that the temperature-sensitive phenotype of a deletion mutation (rpo41Delta2), which impinges on this amino-terminal domain, is suppressed by overproducing Nam1p [2].
• These nuclear genes show no sequence homology to each other and are localized on different chromosomes: NAM1 on chromosome IV, NAM7 on chromosome XIII and NAM8 on chromosome VIII [6].

Anatomical context of MTF2

• These antibodies specifically recognise a 50-kDa protein which purifies along with the mitochondria and corresponds to NAM1p [5].

Regulatory relationships of MTF2

• The NAM1 nuclear gene was shown to control the stability and/or processing of mitochondrial transcripts of the cytochrome b, cytochrome oxidase subunit I and ATP synthase subunit VI genes [Groudinsky O., Bousquet I., Wallis M. G., Slonimski, P. P. & Dujardin G. (1993) Mol. Gen. Genet. 240, 419-427] [5].

Other interactions of MTF2

• How Pet309p may function in concert with other gene products necessary for COX1 RNA translation or accumulation, such as Mss51p or Nam1p, respectively, is discussed [7].
• This was supported by the observation that SLS1 overexpression rescued the petite phenotype of a NAM1 null mutation [8].

Analytical, diagnostic and therapeutic context of MTF2

• To determine which step in mitochondrial RNA metabolism is controlled in vivo by the NAM1 gene, mitochondrial transcripts of seven transcription units from strains carrying an inactive nam1::URA3 gene disruption in various mitochondrial genetic backgrounds were analysed by Northern blot hybridisations [9].
• Sequence analysis of the NAM1 gene shows that it encodes a protein of 440 amino acids with a typical presequence that would target the protein to the mitochondrial matrix [6].

References