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A Jacobson

Publications and source records attributed to A Jacobson.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay.

In the yeast Saccharomyces cerevisiae unstable mRNAs decay 10-20 fold more rapidly than stable mRNAs. In order to examine the basis for the differences in decay rate of the unstable STE3 mRNA and the stable PGK1 and ACT1 mRNAs we have constructed and measured the decay rates of numerous chimeric mRNAs. These experiments indicate that multiple regions within yeast mRNAs are involved in modulating mRNA decay rates. Our results suggest that at least two regions within the STE3 mRNA are involved in stimulating rapid decay. One region is located within the coding region and requires sequences between codons 13 and 179. In addition, the STE3 3' UT can also function to stimulate decay. Surprisingly, the STE3 3' UT is not sufficient to accelerate the turnover of the stable PGK1 transcript unless portions of the PGK1 coding region are first deleted. These results not only identify sequences that function within yeast to stimulate mRNA turnover but also have important implications for an understanding of the basis of differences in eukaryotic mRNA decay rates.

Base Sequence↗
PubMed1992

A coding region segment is necessary, but not sufficient for rapid decay of the HIS3 mRNA in yeast.

In Saccharomyces cerevisiae, the HIS3 (encoding imidazoleglycerolphosphate dehydratase) mRNA is unstable (t1/2 = 7 min), whereas the ACT1 (encoding actin) mRNA is more stable (t1/2 = 30 min). To define determinants responsible for rapid mRNA decay, hybrid genes comprised of various regions of these two mRNAs were constructed, transformed into yeast on centromere-containing vectors, and the half-lives of the resultant chimeric mRNAs were measured. To examine whether the 3'-untranslated region (3'-UTR) of HIS3 can confer instability to the ACT1 mRNA, DNA encoding the 3'-UTR of ACT1 was replaced with the corresponding region of HIS3. The hybrid mRNA containing the HIS3 3'-UTR decayed at a rate similar to the endogenous ACT1 mRNA. The mRNA containing the HIS3 5'-UTR and most of the HIS3 coding region fused to an ACT1 3'-fragment was unstable, indicating that HIS3 instability determinants are located within the HIS3 5'-UTR or coding sequence. Deleting 411 nucleotides (nt) from the coding region of either HIS3 or the 5'-HIS3-ACT1-3' chimeric gene resulted in a three- to fourfold stabilization of the respective mRNAs. However, insertion of this 411-nt fragment in-frame into the entire ACT1 gene had no destabilizing effect on the resultant hybrid mRNA. We conclude that the instability determinants of HIS3 mRNA are complex, involving a coding region segment and, possibly, the 5'-UTR.

Actins↗
PubMed1992

Vertical changes in high-angle Class II, division 1 patients treated with cervical or occipital pull headgear.

Before, after, and 2 years after treatment serial radiographs of two samples of patients with high mandibular plane angle Class II, Division 1 nonextraction who were treated were evaluated retrospectively. One sample comprised patients treated with cervical headgear (CHG), and the other was treated with occipital headgear (OPHG). No significant differences were found when mandibular plane angle or facial height changes, anterior or posterior, were compared. Regarding vertical changes, only maxillary molar height, relative to both sella-nasion and palatal plane, and occlusal plane angle changes were significantly different when cervical and occipital-pull headgear were compared. In both groups of patients, responses to treatment were highly variable and only subtle vertical differences were apparent between mean changes in the cervical and occipital-pull samples.

Adolescent↗
PubMed1992

mRNA stability: in trans-it.

The regulation of mRNA stability is an important step in the control of gene expression. Characterization of the mechanisms involved in the turnover of individual mRNAs has identified a requirement for specific cis-acting sequences and trans-acting factors, as well as an involvement of the translation apparatus. In the past year, significant progress has been made in the identification of trans-acting factors by both biochemical and genetic approaches. This review summarizes that progress and promotes the notion that the ribosome itself should also be considered as a trans-acting component of the mRNA decay machinery.

Animals↗
PubMed1992

Turnover of mRNA in prokaryotes and lower eukaryotes.

The turnover of mRNA plays an important role in the regulation of gene expression. The two best understood model systems are those of the prokaryote Escherichia coli and the lower eukaryote Saccharomyces cerevisiae. Considerable progress in recent years has helped define the general pathways by which mRNA is degraded in E coli. Much less is known about the pathways of decay, or the enzymes involved, in eukaryotic cells. However, both cis-acting sequences and trans-acting factors have recently been characterized in S. cerevisiae and an indispensable role for translation has been identified. A comparison of these model species highlights both similarities and differences in mRNA turnover between prokaryotic and eukaryotic systems.

Bacterial Proteins↗
PubMed1992

A mutation in the tRNA nucleotidyltransferase gene promotes stabilization of mRNAs in Saccharomyces cerevisiae.

To identify trans-acting factors involved in mRNA decay in the yeast Saccharomyces cerevisiae, we have begun to characterize conditional lethal mutants that affect mRNA steady-state levels. A screen of a collection of temperature-sensitive mutants identified ts352, a mutant that accumulated moderately stable and unstable mRNAs after a shift from 23 to 37 degrees C (M. Aebi, G. Kirchner, J.-Y. Chen, U. Vijayraghavan, A. Jacobson, N.C. Martin, and J. Abelson, J. Biol. Chem. 265:16216-16220, 1990). ts352 has a defect in the CCA1 gene, which codes for tRNA nucleotidyltransferase, the enzyme that adds 3' CCA termini to tRNAs (Aebi et al., J. Biol. Chem., 1990). In a shift to the nonpermissive temperature, ts352 (cca1-1) cells rapidly cease protein synthesis, reduce the rates of degradation of the CDC4, TCM1, and PAB1 mRNAs three- to fivefold, and increase the relative number of ribosomes associated with mRNAs and the overall size of polysomes. These results were analogous to those observed for cycloheximide-treated cells and are generally consistent with models that invoke a role for translational elongation in the process of mRNA turnover.

Cycloheximide↗
PubMed1992

Laparoscopic herniorrhaphy.

Laparoscopic preperitoneal prosthetic repair of inguinal and femoral hernias was done in 27 patients, including 18 indirect, nine direct, and two femoral hernias. In four patients bilateral hernias were repaired simultaneously. General anesthesia with endotracheal intubation was used in all patients. Three laparoscopic cannulas were inserted. The peritoneum overlying the internal inguinal ring and floor of Hesselbach's triangle was opened. If an indirect hernia sac was found, it was dissected off the cord structures. A polypropylene prosthesis was used to occlude any potential canal space and to reinforce the pelvic floor. No major operative complications or early recurrences (follow-up, 1-7 months) occurred. Patients were to return to full employment an average of 5 days after surgery (range, 3-7 days).

Hernia, Inguinal↗
PubMed1991

Sequence elements that affect mRNA translational activity in developing Dictyostelium cells.

Post-transcriptional controls, including changes in both mRNA translational activity and stability, play an important role in the regulation of ribosomal protein gene expression in developing Dictyostelium discoideum cells. Previously we have shown that the mechanisms which regulate the translational activity of the r-protein mRNAs operate at the level of translational initiation and do not involve changes in polyadenylation or capping. By analysing the translational behavior of chimeric and mutant mRNAs in transformed cells, we have now been able to localize the determinants of translational activity of one of the r-protein mRNAs to the 5'-untranslated region. Although this and other r-protein mRNAs differ strikingly from the Dictyostelium consensus in the region of the initiator AUG codon, we find that improving the match to that consensus does not increase the translational activity of the message in developing cells. Current experiments are designed to determine whether translational regulation is mediated by strong interactions with specific inhibitors or by weak interactions with translational initiation factors.

Base Sequence↗
PubMed1991

The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon.

mRNA decay rates often increase when translation is terminated prematurely due to a frameshift or nonsense mutation. We have identified a yeast gene, UPF1, that codes for a trans-acting factor whose function is necessary for enhanced turnover of mRNAs containing a premature stop codon. In the absence of UPF1 function, frameshift or nonsense mutations in the HIS4 or LEU2 genes that normally cause rapid mRNA decay fail to have this effect. Instead, the mRNAs decay at rates similar to the corresponding wild-type mRNAs. The stabilization of frameshift or nonsense mRNAs observed in upf1- strains does not appear to result from enhanced readthrough of the termination signal. Loss of UPF1 function has no effect on the accumulation or stability of HIS4+ or LEU2+ mRNA, suggesting that the UPF1 product functions only in response to a premature termination signal. When we examined the accumulation and stability of other wild-type mRNAs in the presence or absence of UPF1, including MAT alpha 1, STE3, ACT1, PGK1, PAB1, and URA3 mRNAs, only the URA3 transcript was affected. On the basis of these and other results, the UPF1 product appears to participate in a previously uncharacterized pathway leading to the degradation of a limited class of yeast transcripts.

Base Sequence↗
PubMed1991

Perceptual organization and focused attention: the role of objects and proximity in visual processing.

The influence of the Gestalt grouping principles of similarity, closure, and proximity on the size of the response-compatibility effect was examined in a focused attention task. In three studies, subjects responded to a centrally located target and attempted to ignore adjacent distractors. The distractors, which served as targets on other trials, could be compatible, incompatible, or neutral with respect to the response of the target. In addition, the distractors and the target could be embedded in the same object, presented in the same color, presented on different objects, or presented in different colors. The typical response-compatibility effect (B. A. Eriksen & C. W. Eriksen, 1974) was found when the target and distractors were embedded in the same object or presented in the same color. Performance was poorer when the target was surrounded by response-incompatible distractors than when it was surrounded by response-compatible distractors. However, the response-compatibility effect was eliminated when the target and distractors were embedded in different objects, even when the distance between the items was less than .25 degrees of visual angle. Furthermore, the response-compatibility effect was of intermediate size when the distractors were not grouped strongly with the target or with neutral flankers. The results are discussed in terms of space- and object-based models of visual attention.

Adolescent↗
PubMed1990

Isolation of a temperature-sensitive mutant with an altered tRNA nucleotidyltransferase and cloning of the gene encoding tRNA nucleotidyltransferase in the yeast Saccharomyces cerevisiae.

We have isolated a yeast mutant, ts352, that is temperature-sensitive for growth. The mutation has a general effect on mRNA metabolism and a specific effect on tRNA biosynthesis. Cells shifted to the nonpermissive temperature accumulate tRNAs that are shorter than mature tRNAs. The increased ability of these tRNAs to accept ATP demonstrates that growth of the ts352 mutant at the nonpermissive temperature results in accumulation of tRNA with defective 3' ends. The activity of ATP (CTP):tRNA-specific tRNA nucleotidyltransferase can readily be measured in extracts from wild type but not mutant cells. We have cloned and sequenced the wild type allele of the ts352 gene and find significant similarity between the yeast protein sequence predicted from the DNA sequence and the protein predicted from the sequence of the Escherichi coli tRNA nucleotidyltransferase gene. Expression of the yeast gene on a multicopy plasmid increases the activity of the tRNA nucleotidyltransferase in extracts. We conclude that the defect in the ts352 mutant is in the gene coding for yeast tRNA nucleotidyltransferase and that we have isolated the yeast gene that codes for this enzyme.

Amino Acid Sequence↗
PubMed1990

Tales of poly(A): a review.

Until recently, evidence to support a translational role for the 3'-poly(A) tract of eukaryotic mRNAs has been mostly indirect, including: a correlation between the adenylation status of individual mRNAs and their translatability in vivo or in vitro, the demonstration that exogenously added poly(A) is a potent competitive inhibitor of the translation of poly(A)+mRNA, but not poly(A)-mRNAs in vitro, and a correlation between the abundance and stability of poly(A)-binding proteins (PABPs) and the rate of translational initiation in vivo. However, more recent studies demonstrate directly that poly(A)+mRNAs can initiate translation more efficiently than poly(A)-mRNAs, and indicate that this effect is: (i) targeted to the formation of 80S initiation complexes, and (ii) likely to be mediated by the cytoplasmic PABP. We suggest that the 3'-poly(A) tail should be considered a translational enhancer which may stimulate translational initiation in much the same way that transcriptional enhancers are thought to stimulate transcriptional initiation.

Animals↗