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Query: UNIPROT:P06889 (Mol)
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Activation of the CYC1 upstream activation site, UAS2, and transcription of several other genes encoding respiratory functions requires the product of the regulatory gene HAP2. We report here the isolation and characterization of a second UAS2 regulatory gene, HAP3. Like mutations in HAP2, a mutation in HAP3 abolishes the activity of UAS2 and prevents growth on nonfermentable carbon sources. The HAP3 gene was cloned and, surprisingly, was found to encode two divergently transcribed, overlapping transcripts: a 570-base RNA and a 3-kilobase (kb) RNA. Chromosomal disruption experiments defined the critical region for HAP3 function to a 1.3-kb segment in which the two transcripts overlap. Analysis of the HAP3 DNA sequence showed that the 570-base transcript could encode a protein of 144 amino acids. Synthesis of the 144-amino-acid protein under regulatory control in vivo demonstrated that this protein is essential for activity of UAS2 as well as for growth on nonfermentable carbon sources. The largest open reading frame in the critical region of the 3-kb transcript is only 86 amino acids. Using site-directed mutagenesis, we demonstrated that the 86-amino-acid open reading frame was not involved in UAS2 activity. The possible role of this 3-kb antisense RNA in HAP3 expression or function is discussed.
Mol Cell Biol 1988 Feb
PMID:The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts. 283 32

A predominantly pyrimidine-rich sequence (purine in the template strand, 32 of 37 bases) is located between a functional TATA element and the corresponding transcription start site region of the Saccharomyces cerevisiae iso-1-cytochrome c (CYC1) gene. By using linker deletions and gene fusion techniques, the functional characteristics of this pyrimidine sequence were examined. Results indicate that the function of this element is to limit the accumulation of full-length mRNAs with 5' ends which map upstream of the pyrimidine-rich sequence. Data suggest that the 5'-noncoding region of the CYC1 gene possesses signals for mRNA 3'-end processing.
Mol Cell Biol 1988 Mar
PMID:Functional characterization of a pyrimidine-rich element in the 5'-noncoding region of the yeast iso-1-cytochrome c gene. 283 56

The mRNA sequence and structures that modify and are required for translation of iso-1-cytochrome c in the yeast Saccharomyces cerevisiae were investigated with sets of CYC1 alleles having alterations in the 5' leader region. Measurements of levels of CYC1 mRNA and iso-1-cytochrome c in strains having single copies of altered alleles with nested deletions led to the conclusion that there is no specific sequence adjacent to the AUG initiator codon required for efficient translation. However, the nucleotides preceding the AUG initiator codon at positions -1 and -3 slightly modified the efficiency of translation to an order of preference similar to that found in higher cells. In contrast to large effects observed in higher eucaryotes, the magnitude of this AUG context effect in S. cerevisiae was only two- to threefold. Furthermore, introduction of hairpin structures in the vicinity of the AUG initiator codon inhibited translation, with the degree of inhibition related to the stability and proximity of the hairpin. These results with S. cerevisiae and published findings on other organisms suggest that translation in S. cerevisiae is more sensitive to secondary structures than is translation in higher eucaryotes.
Mol Cell Biol 1988 Apr
PMID:mRNA structures influencing translation in the yeast Saccharomyces cerevisiae. 283 49

In Saccharomyces cerevisiae, the two genes, CYC1 and CYC7, that encode the isoforms of cytochrome c are expressed at different levels. Oxygen regulation is mediated by the expression of the CYP1 gene, and the CYP1 protein interacts with both CYC1 upstream activation sequence 1 (UAS1) and CYC7 UASo. In this study, the homology between the CYP1-binding sites of both genes was investigated. The most noticeable difference between the CYC1 and CYC7 UASs is the presence of GC base pairs at the same positions in a repeated sequence in CYC7 compared with CG base pairs in CYC1. Directed mutagenesis changing these GC residues to CG residues in CYC7 led to CYC1-like expression of CYC7 both in a CYP1 wild-type strain and in a strain carrying the semidominant mutation CYP1-16 which reverses the oxygen-dependent expression of the two genes. Our results strongly support the hypothesis that the CYP1-binding sites in CYC1 and CYC7 are related forms of the same sequence and that the CYP1-16 protein has altered specificity for the variant forms of the consensus sequences in both genes.
Mol Cell Biol 1988 Jun
PMID:Oxygen-dependent upstream activation sites of Saccharomyces cerevisiae cytochrome c genes are related forms of the same sequence. 284 77

The nucleotide changes associated with both forward and reverse mutations at the CYC1 locus in the yeast Saccharomyces cerevisiae have been investigated by sequencing the mutated gene product, iso-1-cytochrome c and, more directly, by sequencing appropriate DNA segments. Although the majority of these mutations are the result of single base-pair changes, approximately 10% are the result of multiple mutations and these occur predominantly at certain sites and with certain patterns. Most multiple base-pair changes occur within 20 nucleotides of each other and are generally within six nucleotides. On the basis of the frequencies and patterns of mutations, these nucleotide changes are considered to have occurred as single, concerted events, rather than as multiple independent mutations. Analysis of these mutations indicates that multiple base-pair changes can arise by widely differing mechanisms. We have recognized the following classes of mutations: multiple base-pair changes that yield (1) direct repeats or (2) inverted repeats of local DNA sequences; (3) substitutions of two tandem base-pairs; (4) frameshift and contiguous single base-pair substitutions; and (5) recombination of the CYC1 gene with a non-allelic gene, resulting in alterations within contiguous segments that can be over 150 nucleotides in length. Some of the multiple base-pair changes do not fall into any of these categories. We suggest mechanisms to account for each of these five classes.
J Mol Biol 1988 Jun 05
PMID:Multiple base-pair mutations in yeast. 284 49

In the yeast Saccharomyces cerevisiae the CYP1 gene that modulates the expression of iso1-(CYC1) and iso2-cytochrome c (CYP3) structural genes gives rise to two classes of mutated alleles; one class, represented by CYP1-18, has opposite effects on CYC1 and CYP3, it reduces the expression of CYC1 while it stimulates that of CYP3. The other class, represented by cyp1-23 or the related allele hap1-1, reduces the expression of both CYC1 and CYP3 genes. Genetic data suggested that the CYP1 product is a positive regulator of the cytochrome c genes. The CYP1-18 allele has been cloned. We show here that the iso2 overproducer function of CYP1-18 is included in a 5300 base XhoI-PstI fragment. The sequence of this fragment reveals a unique, long, uninterrupted open reading frame of 4449 nucleotides able to encode a protein of 1483 amino acid residues. The predicted product of this open reading frame contains several interesting features. The N-terminal part of the protein resembles a nucleic acid-binding domain, in which two domains can be distinguished. The first is similar to a "finger" DNA binding motif, as found in TFIIIA and other regulatory proteins. The second consists of seven tandemly repeated sequences with a KCPVDH motif. Because of its structure, it is tempting to speculate that this region may act as a "redox sensor" folded around a metal atom or heme and involved in recognition of respiratory effectors. These two domains are separated by an "opa" sequence of 13 Gln residues. Implication of these domains for the function of CYP1-18 is discussed.
J Mol Biol 1988 Nov 20
PMID:CYP1 (HAP1) regulator of oxygen-dependent gene expression in yeast. I. Overall organization of the protein sequence displays several novel structural domains. 285 58

In the accompanying paper, we present and analyse the sequence of a "superactivator" mutant allele of the CYP1 (HAP1) gene. This locus encodes a trans-acting pleiotropic positive regulator of the transcription of both isocytochrome c structural genes. In this paper, we present the genetic localization of the mutation and the sequence of the wild-type fragment that includes the mutation. The mutated phenotype that commutes the expression of the two isocytochrome structural genes (superactivation of CYP3 and inhibition of CYC1) results from a transversion in an AGT codon (serine) in the wild-type to an AGG codon (arginine) in the mutant. Moreover, we show that the missense mutation that affects the amino acid preceding the first cysteine of the "Zn finger" is responsible on its own account for the entire mutated phenotype. In all seven yeast regulatory proteins analysed so far, this position is occupied by a neutral amino acid (serine, alanine or glycine), thus the serine-arginine replacement is a radical one. This result is consistent with the hypothesis of alternative and mutually exclusive Zn fingers, formed either at low or high redox potential, recognizing the target sequences identified in the upstream regions of the CYC1 and CYP3 isocytochrome c structural genes.
J Mol Biol 1988 Nov 20
PMID:CYP1 (HAP1) regulator of oxygen-dependent gene expression in yeast. II. Missense mutation suggests alternative Zn fingers as discriminating agents of gene control. 285 59

The expression of the Saccharomyces cerevisiae CYC1 gene, which encodes iso-1-cytochrome c, produces a family of messenger RNAs whose 5' ends map in the region from position +7 to -93 relative to the first nucleotide at position +1 of the protein-coding DNA sequence. The mechanism of transcription initiation of the CYC1 gene has been examined by using linker-scanning deletions and gene fusions. The various CYC1 derivatives with mutations in the 5' non-coding region were constructed, reintroduced into yeast using a multicopy plasmid, and the mRNA starts mapped by primer extension. The results indicate that four, and possibly five T-A-T-A sequences are located within the 5' non-coding region of the CYC1 gene, and that each T-A-T-A is required for a specific subset of mRNA starts. This conclusion has been confirmed by oligonucleotide mutagenesis of a chromosomal CYC1 T-A-T-A sequence. A loose spatial relationship also exists between the T-A-T-A sequences and the mRNA start sites, and this distance relationship varies from 100 to 60 base-pairs (+/- 15 base-pairs).
J Mol Biol 1986 Feb 05
PMID:Transcription initiation of the Saccharomyces cerevisiae iso-1-cytochrome c gene. Multiple, independent T-A-T-A sequences. 300 31

Chromosomal rearrangements associated with one Ty1 element in the iso-1-cytochrome c (CYC1) region of Saccharomyces cerevisiae yeast cells were examined. Most of the rearrangements were deletions of the three linked genes, CYC1, OSM1, and RAD7, and resulted from recombination involving the single Ty1 element and a solo delta in the same orientation. These deletions differed by the number of Ty1 elements (zero, one, or two) remaining after deletion and by restriction site heterogeneities associated with these elements. A single Ty1 element remained at the deletion junction point much more frequently than no Ty1. Apparently the Ty1-associated delta element nearer to the solo delta was involved more often in recombination than the more distal Ty1-associated delta element. The restriction site data implicate gene conversion and suggest that site-specific recombination within the deltas, if occurring, is not the only mechanism of delta-delta recombination. Three other rearrangements bore deletions which began at the end of the Ty1 element and extended into regions not bearing Ty1 or delta sequences. Two of these deletions eliminated 7 kilobases of DNA, although they differed by an associated reciprocal translocation. The third involved a deletion of 14.7 kilobases of DNA associated with an overlapping inversion.
Mol Cell Biol 1985 Dec
PMID:Deletions extending from a single Ty1 element in Saccharomyces cerevisiae. 301 20

The CYC1-239-O mutation in the yeast Saccharomyces cerevisiae produces a -His-Leu- replacement of the normal -Ala-Gly- sequence at amino acid positions 5 and 6, which lie within a dispensable region of iso-1-cytochrome c; this mutation can accommodate the formation of a hairpin structure at the corresponding site in the mRNA. The amount of the altered protein was diminished to 20% of the wild-type level, whereas the amount of the mRNA remained normal. However, in contrast to the normal CYC1+ mRNA that is associated mainly with four to seven ribosomes, the bulk of the CYC1-239-O mRNA is associated with one to four ribosomes. These results suggest that the stable secondary structure within the translated region of the CYC1 mRNA diminishes translation by inhibiting elongation.
Mol Cell Biol 1985 Aug
PMID:A mutation allowing an mRNA secondary structure diminishes translation of Saccharomyces cerevisiae iso-1-cytochrome c. 301 30


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