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PubMed1994

Sequence of the essential early region of phi C31, a temperate phage of Streptomyces spp. with unusual features in its lytic development.

The temperate phage phi C31 is the most studied bacteriophage infecting Streptomyces spp., and has been used to develop an extensive and widely used series of cloning vectors. The sequence of 10 kb of phi C31 DNA containing most or all of the essential early genes was determined. Among the ORFs, 14 (perhaps 15) appear to be protein-coding, and these have been designated ORF1 to ORF14 and ORFX. Previously mapped transcripts appear to initiate upstream from ORFs 1, 8, 11 and 12, and within ORF3 and ORF12, in each case close to one example of the unusual ('21-mer') sequences that appear to serve as a recognition site for RNA polymerase early in the phi C31 lytic cycle [Ingham et al., Mol. Microbiol. 9 (1993) 1267-1274]. Further copies of the 21-mer are upstream from ORF2 and ORF13. There are four recognisable examples of a conserved inverted repeat sequence motif (CIR) thought to bind phi C31 repressor [Smith and Owen, Mol. Microbiol. 5 (1991) 2833-2844]. Only one CIR is closely associated with a 21-mer sequence, though three are located between known transcription units. Of all 14 ORFs, only one (ORF11) would encode a protein unmistakably resembling other known proteins; its product appears to be a DNA polymerase. Strikingly, two codons, TTA (Leu) and AGG (Arg), are absent from the 14 ORFs.

Amino Acid Sequence↗
PubMed1989

Gene expression in regenerating liver in relation to cell proliferation and stress.

When hepatocyte proliferation is stimulated in the liver by partial hepatectomy, messenger RNAs coding for fibrinogen, actin, c-myc and topoisomerase I are rapidly accumulated. We distinguish an early phase of accumulation (0-3 h after partial hepatectomy) which is also observed after a sham operation for the four genes, and during inflammation produced by Freund's adjuvant in the case of fibrinogen and c-myc genes. The hepatic response to inflammation appears therefore to mimic events characteristic of the G0/G1 transition, such as the accumulation of the c-myc mRNA. The late phase of mRNA accumulation (beyond 3 h after partial hepatectomy) is typical of liver regeneration. The level of c-myc mRNA is transiently increased (20-fold over normal) 20 h after partial hepatectomy, that is, at the time of DNA synthesis. Topoisomerase-I mRNA level increases between 3 and 24 h after partial hepatectomy (5-10-fold over normal). These results suggest that accumulation of c-myc and topoisomerase-I mRNAs is associated with DNA replication in regenerating liver.

Actins↗
PubMed1990

The Balbiani ring 3 gene in Chironomus tentans has a diverged repetitive structure split by many introns.

A set of approximately 15 secretory proteins is synthesized by the salivary gland cells in the midge Chironomus tentans. These proteins are secreted but do not form insoluble fibers until they are transported out of the gland lumen. A Balbiani ring (BR) gene family consisting of four genes (BR1, BR2.1, BR2.2 and BR6) have previously been shown to encode four of these proteins, sp-I a to d, with relative molecular weights of 1 x 10(6). Each BR gene contains an uninterrupted block in which about 100 repeats are tandemly arranged. The repeats are virtually identical and efficient homogenization mechanisms must operate within each block. Here we describe a new BR gene, the BR3 gene, which according to structural similarities may belong to the BR gene family, but at the same time exhibits a strikingly different structure. The gene encodes a 10.9 kb transcript that contains 38 introns and is spliced into a 5.5 kb mRNA. The mRNA is translated into a cysteine-rich 185 kDa major component of the gland secretion. The coding sequence in the gene is built from diverged repeats in which mainly the cysteine codons are preserved and the sequence is split by the introns into 17 to 678-bp long exons. The introns are located at defined positions in relation to the repeat structure. In sharp contrast to the uninterrupted array of identical repeats in the BR1-BR6 genes, the repeats in the BR3 gene are not efficiently homogenized and have diverged extensively from each other. We propose that the splitting of the repeat structure into variable sized exons prevents homogenizations dependent on unequal aligning of homologous sequences.

Amino Acid Sequence↗
PubMed1994

A composite intragenic silencer domain exhibits negative and positive transcriptional control of the bone-specific osteocalcin gene: promoter and cell type requirements.

The osteocalcin (OC) silencer is a unique example of exonic sequences contributing to negative transcriptional control of mammalian gene expression. In this paper we demonstrate, using a reporter transfection assay, that multiple elements reside within the OC +24/+151 domain. Thirty-fold repression is mediated by the +49/+104 fragment, experimentally relocated 3' of the poly(A) signal. Deletion of either the +49/+54 protein-coding sequence or the +98/+104 intronic part of this fragment results in loss of repression activity, suggesting a bipartite organization of the +49/+104 silencer. Of particular interest, we have mapped an antisilencer activity to the ACCCTCTCT motif (+40/+48), found in silencers associated with several other genes. Extension of the +49/+104 silencer to include the +24/+48 and/or the +105/+151 sequences results in increased silencer activity up to 170-fold, suggesting the presence of additional silencer elements within these sequences. The activity of the silencer contained within the +24/+151 OC sequence is directed to the basal promoter and is not dependent on 5' distal enhancer elements, including those that mediate responsiveness of OC transcription to vitamin D. The OC silencer represses the heterologous thymidine kinase promoter and is operative in osseous (normal diploid osteoblasts, ROS 17/2.8 osteosarcoma) as well as HeLa cells. Our results, which suggest the presence of at least five regulatory elements downstream of the OC transcription start site, indicate the complexity of sequences that mediate repression of OC promoter activity.

Base Sequence↗
PubMed1991

Targeting the Escherichia coli lac repressor to the mammalian cell nucleus.

We have previously shown that about 90% of total Escherichia coli lac repressor synthesized in mammalian cells is located in the cytoplasm [Hu and Davidson, Cell 48 (1987) 555-566]. To target a functional lac repressor to the nucleus, we mutated 10 nucleotides at the 3' end of the coding sequence, thus adding the nuclear localization signal of the simian virus 40 large-T antigen to the C terminus of the repressor. The mutant lacI gene and the wild-type (wt) gene, both in standard animal cell expression vectors, driven by the promoter of the Rous sarcoma virus long terminal repeat, were stably transfected into three rodent cell lines. In confirmation of our previous results, only about 10% of the wt repressor, but all of the mutant protein, was localized in the nucleus. DNase I footprint analyses showed that the mutant repressor retained the same operator DNA-binding specificity as wt repressor. Furthermore, both repressor-operator complexes could be dissociated by addition of isopropyl-beta-D-thiogalactopyranoside in vitro. However, the ratio of number of repressor molecules per nucleus that, by in vitro assay, could bind to the operator sequence to the number of monomer repressor polypeptides per nucleus, as determined by Western blotting, was about 1:4 for the wt repressor and about 1:30 for the mutant repressor. This suggests that: (a) the mutant repressor assembles into tetramers inefficiently; and/or (b) it has reduced binding affinity to the operator sequence; and/or (c) it has higher binding affinity to nonspecific DNA.

Antigens, Viral, Tumor↗
PubMed1994

PC12 variants deficient in norepinephrine transporter mRNA have wild type activities of several other related transporters.

Wild type PC12 pheochromocytoma cells express a Na(+)-dependent norepinephrine transporter that operates in the uptake of catecholamines. In addition to the previously described Na(+)-dependent system A for the uptake of alpha-amino-isobutyric acid and system Gly for glycine, we have identified two other Na(+)-dependent transporter systems for amino acid uptake in these cells: 1) system beta for beta-alanine and taurine; and 2) a system for creatine. Uptake of alpha-amino-isobutyric acid, glycine, beta-alanine, and creatine is not affected in some PC12 variants that were previously shown to be deficient in catecholamine uptake and to have decreased levels of norepinephrine transporter mRNA. We have isolated two PC12 cDNA clones that are essentially identical in sequence to recently reported cDNAs for rat brain taurine and creatine transporters, respectively, and a third cDNA that appears to code for a novel transporter. mRNAs for these three transporters are present at wild type levels in those variants that express no or little norepinephrine transporter mRNA. These results support the notion that the expression of catecholamine reuptake transporters may be particularly susceptible to down-regulation.

Amino Acids↗
PubMed1990

Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours.

The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma.

Amino Acid Sequence↗
PubMed1992

Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen.

Cardiac hypertrophy induced by pressure overload is accompanied by increases in the deposition of extracellular matrix (ECM) proteins. We wanted to determine in this study whether changes in mRNA coding for transforming growth factor (TGF)-beta 1, TGF-beta 3, and the ECM proteins, fibronectin and collagen, occur during the early phases of cardiac hypertrophy. Steady-state mRNA levels were determined in sham-operated and thoracic-banded hypertrophied rat myocardium from 6 h to 30 days after surgery. TGF-beta 1 mRNA increased significantly (1.7-fold vs. control) 12 h after aortic banding, decreasing to control levels by 14 days. No significant changes were observed for TGF-beta 3 message. Fibronectin mRNA levels increased twofold at day 1 and peaked to approximately threefold at day 3. Type I and III collagen mRNA expression was similar to control levels at day 1 but increased significantly 3 days after banding. Cardiac hypertrophy also resulted in an induction of mRNA for an embryonic isoform of fibronectin (EIIIA+) that is generated through alternative splicing of the gene. These findings indicate that, with myocardial hypertrophy, mRNAs for fibronectin are increased as early as 1 day after banding, which may allow for an initial increase in the production of fibronectin followed by the deposition of collagen. These increased mRNA levels for the ECM proteins are preceded by marked increases in TGF-beta 1 mRNAs.

Animals↗
PubMed1991

Colocalization of neurotransmitters analyzed by in situ hybridization.

In situ hybridization and Northern blot analysis has been used to analyse in some detail the localization and regulation of the messenger molecules adrenaline, noradrenaline and neuropeptide tyrosine (NPY) within cells of the sympathetic nervous system and the adrenal medulla. In the rat adrenal gland, a novel NPY containing population of ganglion cells was found. Synthetic oligonucleotide probes complementary to mRNA coding for the catecholamine synthesizing enzymes phenylethanolamine N-methyltransferase (PNMT), tyrosine hydroxylase (TH) and NPY were used to analyse the regulation of these genes following administration of the catecholamine depleting drug reserpine. Twenty-four hours after a single dose of reserpine, a differential regulation of PNMT, TH and NPY was found. Thus, a dramatic decrease in PNMT mRNA was observed in the adrenal medulla. In contrast, mRNA for both TH and NPY exhibited an increase. Different regulatory mechanisms may thus operate for these three compounds coexisting in chromaffin cells of the adrenal medulla. The regulation of enzymes and peptides was also studied in human sympathetic ganglia. After brief electrical preganglionic stimulation of thoracic ganglia in humans, in situ hybridization was performed with synthetic oligonucleotide probes complementary to TH, dopamine beta-hydroxylase (DBH) and NPY mRNA respectively. A several fold increase in all three mRNAs was found in the principal ganglion cells. The results point to a very rapid regulation of genes involved in signal transmission in the sympathetic nervous system of humans. The results also suggest a novel way to define neuronal projections by visualizing increases in mRNA levels following electrical stimulation.

Adrenal Glands↗
PubMed1988

Search for a scrapie-specific nucleic acid: a progress report.

Scrapie agent contains a proteinaceous component as well as an 'informational' molecule (suggested by the existence of distinct strains of scrapie). These operationally defined entities may be the same molecule, an infectious protein, or distinct, in which case a nucleic acid might encode the genetic information. Purification of scrapie agent enriched a protein, PrPSc, by virtue of its relative protease resistance. There is only a single PrP gene and the primary translation product of PrP mRNA is the same in normal and scrapie-infected brain; therefore the normal PrPC and the protease-resistant isoform, PrPSc, found in scrapie, probably result from different post-translational events. To search for scrapie-specific nucleic acid, globin RNA made in vitro was added to highly purified infectious preparations at a ratio of 10(3) molecules per infectious unit, nucleic acids were isolated and denatured, and cDNA synthesized using random oligonucleotide primers. Clones containing globin-related sequences were identified by in situ hybridization. 150 plaques not hybridizing to the globin probe were isolated. Inserts larger than 50 base pairs were analysed. By hybridization to a globin probe at reduced stringency all but four clones were found to contain small globin related inserts; two of these hybridized to hamster repetitive sequences as shown by Southern blot analysis. The other clones not related to hamster nucleic acids may be derived from unknown sources of contamination or from scrapie-specific nucleic acids.

Animals↗
PubMed1989

[Left ventricular accumulation of messenger ribonucleic acid coding for the natriuretic atrial factor in various experimental models of cardiac hypertrophy in rats].

Cardiac hypertrophy secondary to chronic hemodynamic overload is associated with an increase in the ventricular concentration of the messenger ribonucleic acid (mRNA) coding for the atrial natriuretic factor (ANF). We have compared, in male Wistar rats (10 week old, 200-220 g), using dot blot hybridization and a specific oligonucleotide probe, the left ventricular concentration of ANF mRNA (LV ANF mRNA) in 4 models of chronic hemodynamic overload inducing various patterns of left ventricular hypertrophy (LVH): a model of volume overload, the aortocaval fistula (ACF, n = 15); a model of pressure overload, coarctation of the abdominal aorta (CoA, n = 13) and 2 models of mixed overload, aortic regurgitation (AR, n = 7) and myocardial infarction (INF, n = 18). A month after surgery, LVH was 49 p. 100 for AR, 41 p. 100 for Co A and 21 p. 100 for ACF. Instead of a severe infarction, LVH was 6 p. 100 in INF demonstrating a marked hypertrophy of the non infarcted myocardium. For each model, LV ANF mRNA was compared to that in a corresponding group of sham-operated control rats and expressed as the percentage of ANF mRNA concentration in the pooled atria of the controls. In the 4 control groups LV ANF mRNA was 1 +/- 0.5 p. 100 that in the corresponding atria and the sham-operated animals were thus pooled in a single group (n = 19). In the 4 models of LVH, LV ANF mRNA markedly increased as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli.

The Escherichia coli gene thrS that codes for threonine-tRNA ligase (tRNAThr ligase, formerly threonine-tRNA synthetase, EC 6.1.1.3) has previously been shown to be negatively autoregulated at the level of translation. Here we describe the use of several thrS-lac gene fusions to isolate cis-acting regulatory mutations that increase the translation but not the transcription of the thrS gene. These mutations lead to a total loss of control of repression and derepression of thrS. DNA sequence analysis locates the mutations between 10 and 40 base pairs upstream of the translation initiation codon of thrS and more than 100 base pairs downstream of the transcription initiation site. The mRNA region where these mutations are located shares primary and secondary structure homologies with specific parts of several isoacceptor tRNAThr species. These findings suggest that the ligase regulates its translation by binding to its mRNA at a place that shares some homology with its natural substrate.

Amino Acyl-tRNA Synthetases↗
PubMed1990

Changes in messenger RNAs coding for neurotransmitter receptors and voltage-operated channels in the developing rat cerebral cortex.

The ontogenetic development of poly(A)+ mRNAs coding for receptors to several neurotransmitters (kainate, glutamate, acetylcholine, and serotonin) and voltage-operated channels (sodium and calcium) was studied by isolating total poly(A)+ mRNA from the brains of rats at various developmental stages and injecting it into Xenopus oocytes. The oocytes translated the foreign mRNA and incorporated functional receptor/ion channel complexes into the cell membrane. Thus, recording of induced membrane currents in voltage-clamped oocytes gave a measure of the relative amounts of the different messengers. Responses induced by kainate, glutamate, acetylcholine, and serotonin all increased with age and reached a maximum in oocytes injected with mRNA from adult cortex. Messenger RNAs for the earliest ages examined, Embryonic Days 15 and 18, expressed little or no response to kainate, glutamate, or acetylcholine, while 50-70% of the adult response was reached by Postnatal Day 10. In contrast, the serotonin-induced response was already comparatively large (16% of the adult level) in oocytes injected with mRNA from Embryonic Day 15 brain and increased postnatally to adult levels. The expression of voltage-dependent sodium and calcium channels was small in oocytes injected with mRNA from embryonic animals and increased postnatally to reach a maximum in oocytes injected with mRNA from adult animals.

Aging↗
PubMed1985

Multisequence comparisons in protein coding genes. Search for functional constraints.

A very powerful method for detecting functional constraints operative in biological macromolecules is presented. This method entails performing a base permanence analysis of protein coding genes at each codon position simultaneously in different species. It calculates the degree of permanence of subregions of the gene by dividing it into segments, c codons long, counting how many sites remain unchanged in each segment among all species compared. By comparing the base permanence among several sequences with the expectations based on a stochastic evolutionary process, gene regions showing different degrees of conservation can be selected. This means that wherever the permanence deviates significantly from the expected value generated by the simulation, the corresponding regions are considered "constrained" or "hypervariable". The constrained regions are of two types: alpha and beta. The alpha regions result from constraints at the amino acid level, whereas the beta regions are those probably involved in "control" processing. The method has been applied to mitochondrial genes coding for subunit 6 of the ATPase and subunit 1 of the cytochrome oxidase in four mammalian species: human, rat, mouse, and cow. In the two mitochondrial genes a few regions that are highly conserved in all codon positions have been identified. Among these regions a sequence, common to both genes, that is complementary to a strongly conserved region of 12S rRNA has been found. This method can also be of great help in studying molecular evolution mechanisms.

Amino Acid Sequence↗
PubMed1985

Effects of heterologous ribosomal binding sites on the transcription and translation of the lacZ gene of Escherichia coli.

A vector (pKL203) was constructed which contains the promoter-operator region of the lacZ gene and the major part of the coding sequence of the lac operon. The lacZ translation initiation signals [Shine-Dalgarno (SD) sequence and AUG codon] were deleted, and in their place a synthetic linker sequence was inserted, providing single restriction sites for SmaI and BamHI. With this vector constructions were made in which initiation signals of other prokaryotic genes (phage MS2 maturation protein, phage Q beta A2 gene and tufB gene) were fused to the lacZ gene, giving rise to various fusion proteins. The introduction of N-terminal amino acids (aa) in beta-galactosidase (beta-gal) which differ from the wild-type aa invariably leads to an enzyme with a strongly reduced thermostability as compared to the wild-type enzyme. Therefore an immunoprecipitation method was used to measure the amount of fusion protein. It was found that these amounts varied strongly from one construction to another. Concomitant determinations of the amounts of lac-operon-specific mRNA showed an unexpectedly large variation among the clones. No strict correlation could be found between the level of lac mRNA and beta-gal production. Per molecule of lac mRNA, translation appears to be most efficient when the homologous lacZ initiation signal is present.

Binding Sites↗
PubMed1980

Novel features in the genetic code and codon reading patterns in Neurospora crassa mitochondria based on sequences of six mitochondrial tRNAs.

We report the sequences of Neurospora crassa mitochondrial alanine, leucine(1), leucine(2), threonine, tryptophan, and valine tRNAs. On the basis of the anticodon sequences of these tRNAs and of a glutamine tRNA, whose sequence analysis is nearly complete, we infer the following: (i) The N. crassa mitochondrial tRNA species for alanine, leucine(2), threonine, and valine, amino acids that belong to four-codon families (GCN, CUN, ACN, and GUN, respectively; N = U, C, A, or G) all contain an unmodified U in the first position of the anticodon. In contrast, tRNA species for glutamine, leucine(1), and tryptophan, amino acids that use codons ending in purines (CA(G) (A), UU(G) (A), and UG(G) (A), respectively) contain a modified U derivative in the same position. These findings and the fact that we have not detected any other isoacceptor tRNAs for these amino acids suggest that N. crassa mitochondrial tRNAs containing U in the first position of the anticodon are capable of reading all four codons of a four-codon family whereas those containing a modified U are restricted to reading codons ending in A or G. Such an expanded codon-reading ability of certain mitochondrial tRNAs will explain how the mitochondrial protein-synthesizing system operates with a much lower number of tRNA species than do systems present in prokaryotes or in eukaryotic cytoplasm. (ii) The anticodon sequence of the N. crassa mitochondrial tryptophan tRNA is U(*)CA and not CCA or CmCA as is the case with tryptophan tRNAs from prokaryotes or from eukaryotic cytoplasm. Because a tRNA with U(*)CA in the anti-codon would be expected to read the codon UGA, as well as the normal tryptophan codon UGG, this suggests that in N. crassa mitochondria, as in yeast and in human mitochondria, UGA is a codon for tryptophan and not a signal for chain termination. (iii) The anticodon sequences of the two leucine tRNAs indicate that N. crassa mitochondria use both families of leucine codons (UU(A) (G) and CUN; N = U, C, A, or G) for leucine, in contrast to yeast mitochondria [Li, M. & Tzagoloff, A. (1979) Cell 18, 47-53] in which the CUA leucine codon and possibly the entire CUN family of leucine codons may be translated as threonine.

Anticodon↗
PubMed1989

Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis.

Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.

Animals↗
PubMed1992

Suppression of carboxy-terminal truncations of the yeast mitochondrial mRNA-specific translational activator PET122 by mutations in two new genes, MRP17 and PET127.

The PET122 protein is one of three Saccharomyces cerevisiae nuclear gene products required specifically to activate translation of the mitochondrially coded COX3 mRNA. We have previously observed that mutations which remove the carboxy-terminal region of PET122 block translation of the COX3 mRNA but can be suppressed by unlinked nuclear mutations in several genes, two of which have been shown to code for proteins of the small subunit of mitochondrial ribosomes. Here we describe and map two more new genes identified as allele-specific suppressors that compensate for carboxy-terminal truncation of PET122. One of these genes, MRP17, is essential for the expression of all mitochondrial genes and encodes a protein of M(r) 17343. The MRP17 protein is a component of the small ribosomal subunit in mitochondria, as demonstrated by the fact that a missense mutation, mrp17-1, predicted to cause a charge change indeed alters the charge of a mitochondrial ribosomal protein of the expected size. In addition, mrp17-1, in combination with some mutations affecting another mitochondrial ribosomal protein, caused a synthetic defective phenotype. These findings are consistent with a model in which PET122 functionally interacts with the ribosomal small subunit. The second new suppressor gene described here, PET127, encodes a protein too large (M(r) 95900) to be a ribosomal protein and appears to operate by a different mechanism. PET127 is not absolutely required for mitochondrial gene expression and allele-specific suppression of pet122 mutations results from the loss of PET127 function: a pet127 deletion exhibited the same recessive suppressor activity as the original suppressor mutation. These findings suggest the possibility that PET127 could be a novel component of the mitochondrial translation system with a role in promoting accuracy of translational initiation.

Alleles↗