Disease relevance of VAR1

• In particular, we show that mt-Hsp70 acts in maintaining the var1 protein, the only mitochondrially encoded subunit of mitochondrial ribosomes, in an assembly competent state, especially under heat stress conditions [1].

High impact information on VAR1

• Location and structure of the var1 gene on yeast mitochondrial DNA: nucleotide sequence of the 40.0 allele [2].
• It contains an open reading frame of 396 codons, which we identify as the structural gene for var1 protein [2].
• Furthermore, var1 is an expandable gene that participates in a novel recombinational event resembling gene conversion whereby shorter alleles are preferentially converted to longer ones [3].
• The remarkable features of var1 indicate that it may have evolved by a mechanism analogous to exon shuffling, although no introns are actually present [3].
• In this study, we tested whether chimeric mRNAs with the untranslated sequences normally present on the mRNA encoding soluble Var1p, can direct functional expression of coding sequences specifying the integral membrane proteins Cox2p and Cox3p [4].

Biological context of VAR1

• The relocation of VAR1 from the mitochondrion to the nucleus provides an excellent system for the molecular genetic analysis of structure-function relationships in the unusual Var1 protein [5].
• Respiratory growth was restored in PZ206 mutants by transformation with a centromere plasmid carrying VAR1U under ADH1 promoter control, thus proving that VAR1 function can be relocated from the mitochondrion to the nucleus [5].
• VAR1 is the only yeast mitochondrial gene encoding a major soluble protein [6].
• Competition assays with the cloned 21S-related mt DNA fragment undergoing interaction showed that a sequence in that fragment is present in mt DNA from a rho-strain retaining the 16S mt rRNA gene, but not in a VAR1-retaining rho-strain that lacks cAMP-mediated mt transcription [7].
• We have detected double-strand breaks in the var1 gene in mitochondrial DNA isolated from unmated haploid rho+ and rho- strains at or near the boundaries of the optional GC cluster, as well as at a conserved copy of that sequence 160 base pairs upstream [8].

Anatomical context of VAR1

• However, COXII and VAR1 sequences are 4-to 5-fold more sensitive to DNase I digestion of mtDNA in toluene-permeabilized mitochondria from the delta abf2 mutant than from wild-type cells, but no difference in DNase I sensitivity was detected with the ori5 probe [9].
• The var1 locus of yeast mitochondrial DNA encodes a protein of the small mitochondrial ribosome subunit, denoted var1 protein [10].
• Trans action and the var1 determinant region on yeast mitochondrial DNA. Specific labeling of mitochondrial translation products in zygotes [11].

Associations of VAR1 with chemical compounds

• This observation is consistent with the fact that in yeast, chloramphenicol inhibits mitochondrial protein synthesis by about 95% only and that the synthesis of the var1 protein appears to be the least sensitive to this inhibition [12].

Regulatory relationships of VAR1

• The mitochondrially encoded var1 protein showed enhanced aggregation after synthesis in mdj1 mutant mitochondria [13].

Other interactions of VAR1

• Expression of the oli1 gene, co-transcribed with the var1 gene in primary transcripts, is not affected [14].
• Incorporation of the yeast mitochondrial ribosomal protein Mrp2 into ribosomal subunits requires the mitochondrially encoded Var1 protein [15].

Analytical, diagnostic and therapeutic context of VAR1

• A pair of yeast strains of opposite mating type was constructed to contain polymorphisms at three loci on the mitochondrial genome--the 21 S rRNA gene, var1, and cob--such that parental and recombinant forms of these genes could be easily detected by Southern blot analysis [16].

References