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At least 505 records · Page 28Linked to original sources
PubMed2004

The bipartite 3'-cis-acting signal for replication is required for formation of a ribonucleoprotein complex in vivo between the viral genome and its RNA polymerase in yeast 23 S RNA virus.

23 S RNA narnavirus is a persistent positive strand RNA virus found in Saccharomyces cerevisiae. The viral genome (2.9 kb) encodes only its RNA-dependent RNA polymerase, p104, and forms a ribonucleoprotein complex with p104 in vivo. Previously we succeeded in generating 23 S RNA virus in yeast from an expression vector containing the entire viral cDNA sequence. Using this system, we have recently identified a bipartite 3' cis-acting signal for replication. The signal consists of a stretch of four cytidines (Cs) at the 3' end and a mismatched pair of purines in a stem-loop structure that partially overlaps the terminal four Cs. Although the 3' terminal and penultimate Cs are not essential for virus launching, the generated viruses efficiently recovered these terminal nucleotides. In this work, we expressed RNA transcripts containing the entire 23 S RNA genome but incapable of generating the virus because of the presence of non-viral extra sequences at the 3' ends. These transcripts could form complexes with p104 in vivo, and a detailed analysis indicated that the mismatched pair of purines as well as the third and fourth Cs from the viral 3' end was essential for this complex-forming activity. Given that 23 S RNA virus does not have genes for capsid proteins, the binding of p104 to the viral 3' end, in addition to the efficient 3' terminal repair, may play a crucial role in virus persistence by protecting and maintaining the correct viral 3' end in vivo.

Base Sequence↗
PubMed2006

Microbiology of postoperative infections.

BACKGROUND: Surgical infections, accounting for approximately one quarter of all nosocomial infections, contribute to longer hospital stays and higher medical costs. Clinical failure of antibiotic treatment often is associated with increasing drug resistance. METHODS: Non-duplicated microbial isolates obtained at our institution from surgical patients were identified and tested for antimicrobial susceptibility using the Sceptor system in 2001-2002 and the Phoenix system in 2003-2005. Epidemiologic data were extracted using Epicenter and Powerlab. During selected periods, genetic and biochemical characterization was performed by pulsed-field gel electrophoresis, colony blot hybridization, gene amplification and sequencing, isoelectric focusing, and enzyme kinetics. RESULTS: The specimens were most commonly isolated from infections at surgical sites (24.0%), the urinary tract (19.0%), and blood stream (10.6%). Isolates of Escherichia coli showed an increasing prevalence of resistance to penicillins, third-generation cephalosporins, ciprofloxacin, and gentamicin, whereas the prevalence of resistant Staphylococcus aureus generally declined. Highly aggressive multi-drug-resistant (MDR) Pseudomonas aeruginosa strains were widespread, although colistin remained effective in 100% of cases. A significant increase was seen in infections attributable to S. epidermidis and Candida albicans. The overall number of Enterobacteriaceae carrying extended-spectrum beta-lactamases increased continuously, and new resistance traits emerged. It appeared that the TEM-92 determinant moved from Enterobacteriaceae to nonfermenting gram-negative rods such as Acinetobacter baumannii. CONCLUSION: The number and type of antimicrobial-resistance determinants are increasing.

Anti-Bacterial Agents↗
PubMed2006

Identification and characterization of ceftriaxone resistance and extended-spectrum beta-lactamases in Malawian bacteraemic Enterobacteriaceae.

OBJECTIVES: To enumerate and characterize extended-spectrum beta-lactamases (ESBLs) amongst ceftriaxone-resistant coliforms in Blantyre, Malawi, where third-generation cephalosporin use is currently highly restricted. METHODS: Over the period April 2004-March 2005 all ceftriaxone-resistant isolates from blood cultures were examined for the presence of ESBLs. Isoelectric focusing was performed on enzyme extracts. PCR and DNA sequencing of amplicons were used to identify the underlying genetic determinants responsible for the ESBL phenotypes. Transferability of the ESBL phenotypes was tested by conjugation to a susceptible Escherichia coli J53. RESULTS: Enterobacteriaceae were isolated from 1191 blood cultures, of which 19 (1.6%) were ceftriaxone resistant. Ten isolates (0.7% of all isolates) demonstrated an ESBL phenotype but only eight were characterized as three isolates were from the same patient. Genotypes SHV-11 (n = 1), SHV-12 (n = 3), SHV-27 (n = 1), TEM-63 (n = 2) and CTX-M-15 (n = 1) were detected. Plasmid transfer of the ESBL resistance phenotype was successful for all the isolates. CONCLUSIONS: In a clinical setting of minimal cephalosporin usage there is already a diversity of ESBL genotypes. Increased use of cephalosporins in this setting is likely to result in a rapid expansion of ESBLs and their prevalence will need to be carefully monitored.

Adult↗
PubMed2006

Bioinformatics-driven, rational engineering of protein thermostability.

A longstanding goal in protein engineering is to identify specific sequence changes that endow proteins with desired functional properties. As opposed to traditional rational and random protein engineering techniques, we have employed a bioinformatic approach to identify specific sequence changes that influence key functional properties of a protein within a defined superfamily. Specifically, we have used the Bayesian sequence-based algorithms PROBE and Classifier to identify a strand-turn-strand motif that contributes to thermophilicity among members of the serine protease subtilase superfamily. By replacing a 16 amino acid sequence in the mesophilic subtilisin E (from Bacillus subtilis) with a bioinformatics-generated thermophilic model sequence, the melting temperature of subtilisin E was increased by 13 degrees C. While wild-type subtilisin E was inactive at 90 degrees C, the mutant retained a substantial fraction of its function, with ca. one-third of the activity that it has at 45 degrees C.

Algorithms↗
PubMed1993

Fine specificity of the IgE interaction with the low and high affinity Fc receptor.

The characterization of the site(s) on the IgE molecule that accommodate the high (Fc epsilon RI) and low (Fc epsilon RII) affinity receptors for IgE should allow the design of IgE analogues that can be used to block the onset of the allergic response or to regulate IgE production. To identify the IgE domain responsible for receptor binding, we generated a series of chimeric IgE antibodies in which constant region domains were interchanged between the human and mouse molecules. Binding studies with these chimeras revealed that both the high and low affinity receptor binding-sites reside primarily in the third constant domain of IgE (C epsilon 3). Additional chimeric IgE molecules were generated in which different parts of the human C epsilon 3 domain were exchanged with their murine homologues. Binding experiments with these chimeras suggest that not only the sequence of a particular C epsilon 3 fragment, but the entire C epsilon 3 domain in its native configuration is essential for binding to the Fc epsilon RI. The amino acid residues determining the species specificity of the Fc epsilon RII are not contained in the first 16 amino acids of the C epsilon 3 domain.

Animals↗
PubMed1997

PCR mutagenesis-based method for generation of positive controls for SSCP analysis.

We have developed a primer-mediated PCR mutagenesis-based method for the generation of positive controls to test the sensitivity of single-strand conformation polymorphism (SSCP) or any other PCR-based mutation screening method. This technique is based on the incorporation of a third longer primer, containing a mismatched base, into the PCR along with the two wild-type primers normally used to amplify DNA fragments for SSCP analysis. The longer mismatch primer (LMP) shares the sequence of one of the wild-type primers and also contains 5 to 10 additional bases, which include the mismatched base. The resulting PCR product is identical in length and sequence to the wild-type template with the exception that the LMP base mismatch is incorporated into nearly 100% of the product. We have observed an altered SSCP mobility pattern in all cases where positive controls have been generated using this technique. We believe that the use of such in vitro-generated controls can contribute to the interpretation of band patterns and to the optimization of experimental conditions for SSCP to facilitate maximum detection of sequence variants.

Base Sequence↗
PubMed2001

Chromosomal mapping and organization of the human histamine H3 receptor gene.

The histamine H3 receptor (H3R) was recently cloned, and two isoforms, termed H3L and H3S, differing in the third intracytosolic loop, were isolated but the chromosomal mapping and organization of its gene remained unknown. PCR analysis of a human x rodent cell hybrid panel indicated that the H3R gene is located in the telomeric region of chromosome 20q. Alignment of human H3R cDNA sequences with DNA sequences of this chromosome revealed that its coding region comprises three exons interrupted by two introns located in the second transmembrane domain (TM2) and second intracytosolic loop, respectively. Thus the organization of the H3R gene indicates that the H3L and H3S isoforms, that we characterized not only in rodents but also in humans, are generated by retention and deletion, respectively, of a pseudo-intron located in the third intracytosolic loop.

Animals↗
PubMed2001

Isoelectric focusing nonporous silica reversed-phase high-performance liquid chromatography/electrospray ionization time-of-flight mass spectrometry: a three-dimensional liquid-phase protein separation method as applied to the human erythroleukemia cell-line.

A liquid-phase three-dimensional protein separation method has been developed that is used to separate the cytosolic fraction of a HEL cell lysate via isoelectric focusing (IEF), nonporous silica (NPS) reversed-phase high-performance liquid chromatography (RP-HPLC) and electrospray ionization time-of-flight mass spectrometry (ESI-TOFMS), respectively. Several hundred unique protein molecular weights were observed in a pI range from 4.8 to 8.5 and a mass range from 5 to 85 kDa. Proteins were positively identified by analysis of the pI (+/-0.5 pI units), an intact protein molecular weight (+/-150 ppm), and peptide mass mapping results. Using the molecular weight (MW) and peptide mapping results of identified proteins it was possible to characterize their posttranslational (PTMs) and/or sequence modifications. PTMs were detected on both forms of cytosolic actin, heat shock 90 beta, HINT and alpha-enolase. Sequence modifications or conflicts were observed for beta-and gamma-actin, ATP beta-synthase and heat shock 90 beta. IEF-NPS-RP-HPLC/ESI-TOFMS was used to determine experimental pI, MW and relative hydrophobicity values for each protein detected. This data was used to generate a 2-D pI-MS protein map, where proteins are displayed according to their pI and molecular weight. Protein molecular weight peaks are represented as bands in the 2-D pI-MS image where the gray scale of each band is proportional to the intensity of the protein molecular weight peak. In addition, a third hydrophobicity dimension (%B) was added as the % acetonitrile elution to generate a 3-D pI-MS-%B plot where each protein can be tagged according to three parameters.

Amino Acid Sequence↗
PubMed2001

Cleavage in and around the DR1 element of the A sequence of herpes simplex virus type 1 relevant to the excision of DNA fragments with length corresponding to one and two units of the A sequence.

The A sequence of herpes simplex virus type 1 (HSV-1) is a region bracketed by two direct repeats named DR1. Concatemeric HSV-1 DNA, the product of DNA replication, is cleaved at a specific site on the second DR1 distal from the S component (authentic cleavage) to yield unit-length linear HSV-1 DNA prior to or during packaging of HSV-1 DNA. The presence of two DNA bands, of 0.25 kb (shorter band) and 0.5 kb (longer band), the lengths of which correspond to one and two units of the A sequence, was identified using acrylamide gel electrophoresis of HSV-1 DNA preparations extracted by the method of Hirt. Twelve DNA fragments from each band were molecularly cloned, and nucleotide sequences were determined. Both termini of eight (67%) DNA clones from the shorter band corresponded to the specific cleavage site on DR1. Five (41%) DNA clones from the longer band had a terminus corresponding to the specific cleavage site on DR1 on one side, but not on the opposite side. Thirteen (54%) of 24 termini of 12 analyzed DNA clones from the longer band were in and around DR1. Thus, cleavage events of DR1 can be classified into three categories: (i) authentic cleavage; (ii) site-specific cleavage on the third DR1 distal from the S component (secondary site-specific cleavage), which is related to the generation of the shorter DNA band in combination with authentic cleavage; and (iii) less-specific cleavage events in and around other DR1 elements which relate to the generation of the longer DNA band.

Base Sequence↗
PubMed2000

Sequence and distribution of pro-opiomelanocortin in the pituitary and the brain of the chicken (Gallus gallus).

Although pro-opiomelanocortin (POMC) is a well-known hormone precursor in many species, molecular information about avian POMCs is still relatively scarce. In a former study (Berghman et al., [1998] Mol Cell Endocrinol. 142:119-130) the nucleotide and amino acid sequence of N-terminal POMC in the chicken were reported. To complete the nucleotide sequence of the precursor, rapid amplification of 3' and 5' cDNA end reactions were performed and the polymerase chain reaction (PCR) products were cloned and sequenced. The chicken POMC coding region appears to consist of 678 base pairs in the pituitary and also in the hypothalamus, as assessed by reverse transcriptase PCR. Overall nucleotide sequence homology with other species ranges from 41% (in bovine) to 57% (in rat). The distribution of the POMC mRNA in pituitary and brain was analyzed by in situ hybridization by using 33P-labelled oligonucleotides. Expression of POMC mRNA in the pituitary was restricted to the cephalic lobe, whereas in the brain, the signal was limited to the hypothalamic region. As assessed by Northern blot analysis, the length of the POMC mRNA in both the pituitary and the hypothalamus was approximately 1,200 nucleotides. By using antisera to N-terminal POMC, alpha-melanotropin and beta-endorphin, POMC-containing cells were observed in the cephalic lobe of the pituitary and immunopositive perikarya were localized in the infundibular nucleus and median eminence of the hypothalamus. Immunoreactive fibers were found in the preoptic area and in the medial basal hypothalamus surrounding the third ventricle and more dorsally in the thalamus. Double-staining experiments in the pituitary clearly indicated a complete overlap of the signals generated by these antisera.

Amino Acid Sequence↗
PubMed1991

Mistargeting of peroxisomal L-alanine:glyoxylate aminotransferase to mitochondria in primary hyperoxaluria patients depends upon activation of a cryptic mitochondrial targeting sequence by a point mutation.

In approximately one-third of primary hyperoxaluria type 1 patients, disease is associated with a unique protein sorting defect in which hepatic L-alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44), which is normally peroxisomal, is mistargeted to mitochondria. In all such patients analyzed to date, the gene encoding the aberrantly targeted AGT carries three point mutations, each of which specifies an amino acid substitution. In this paper we show that one of these substitutions, a proline-to-leucine at residue 11, is necessary and sufficient for the generation of a mitochondrial targeting sequence in the AGT protein. AGT with this substitution appears to interact specifically with the mitochondrial protein import machinery, via a discrete N-terminal domain of the AGT protein. The N-terminal 19 amino acids of AGT with this substitution are sufficient to direct mouse cytosolic dihydrofolate reductase to mitochondria, and a synthetic peptide corresponding to this same 19-amino acid region reversibly inhibits mitochondrial protein import, not only of AGT but also of ornithine transcarbamoylase, a genuine cytoplasmically synthesized mitochondrial protein. We have extended these studies to analyze a region of normal human AGT cDNA directly upstream of the coding region. This sequence appears to correspond to an ancestral mitochondrial targeting sequence deleted from the human coding region by point mutation at the initiation codon. We show that reestablishment of this initiation codon produces an active mitochondrial targeting sequence that is different to that found in the hyperoxaluria patients. These results are discussed with reference to the AGT targeting defect in primary hyperoxaluria and also in relation to the highly unusual species specificity of subcellular distribution of AGT among mammals.

Alanine Transaminase↗
PubMed1991

Analysis of sequences regulating larval expression of the Adh gene of Drosophila melanogaster.

The effects of a series of eight, 50 base pair internal deletions in the 5' region upstream of the proximal transcription start site of the Adh gene of Drosophila melanogaster were examined in a quantitative assay. Mixtures of two plasmids, one bearing a deleted gene, the other with an intact reference gene, were injected into alcohol dehydrogenase-negative embryos. Third instar larvae of the injected generation were assayed for relative alcohol dehydrogenase enzyme activity. Quantitative analysis of the eight deletions indicated that two regions were required for any detectable enzyme activity and one region was required for appropriate tissue specificity. The remaining five deletions significantly decreased, but did not eliminate activity. When the deleted genes were placed on a plasmid with an intact reference gene, activities of all but one deletion were restored to levels equivalent to that of the intact reference gene (regardless of orientation). This restoration of activity did not occur when the regulatory region of the intact gene was replaced with the Hsp70 heat shock promoter nor when the 50-base pair deletion encompassed the region that includes the TATA sequence. The fact that seven of the eight deleted genes express activity in the presence of a reference gene on the same plasmid suggests that the deleted gene is controlled by regulatory elements in the reference gene. Further, these regulatory elements exhibit no preference for their own, more proximate, promoter.

Alcohol Dehydrogenase↗
PubMed1999

Difference in strength of autonomously replicating sequences among repeats in the rDNA region of Saccharomyces cerevisiae.

The rDNA region of Saccharomyces cerevisiae contains 100-200 tandemly repeated copies of a 9 kb unit, each with a potential replication origin. In the present studies of cloned fragments from the region involved in the regulation of replication of rDNA, we detected differences in autonomously replicating sequence (ARS) activity for clones from the same yeast strain. One clone, which showed very low ARS activity, carried a point mutation, a C instead of T, in position 9 of the essential 11 bp consensus ARS as compared to clones carrying the normal 10-of-11-bp match to the consensus. The mutation could be traced back to genomic rDNA where it represents about one-third of the rDNA units in that strain. Differences in ARS activity have implications for understanding the regulation of replication of rDNA, and the ratio of active to inactive ARS in the rDNA region may be important for potential generation of extrachromosomal copies.

Base Sequence↗
PubMedDate not supplied

[A distinctive scheme of amino acid replacement was evolved for the generation of diversity, among hypervariable positions (author's transl)].

The diversity of amino acid residues, at a same position when comparing several aligned polypeptide sequences, may be translated as follows. The way along which a given amino acid, A, is replaced--in average--by another amino acid, B, is characterized by a coefficient linked with the pair A-B. Thus, one given amino acid is given a "set" of 19 coefficients, and the 20 different such sets may be analyzed. This method applies to the analysis of the diversity, among different sequences VH and VL of the variable regions of immunoglobulin heavy chains and light chains. From an observation of the alterations of those different sets, according to the sample of positions from which they were derived, it is possible to reach to the following conclusions. A) In the first approximation, all the amino acids present the same behaviour, whichever the sample. The frequency of replacement of an amino acid, A, by another amino acid B, is mainly a function of the proportion of B in the sample. B) In the second approximation, a more elaborate scheme of replacement is apparent, and is linked with an equivalent scheme in the genetic code; it is shown that hypervariable positions as well as random positions in VH and VL obey to this scheme. C) In the third approximation, a complementary structure is observed, which only pertains to the sample of hypervariable positions, and which might constitute a peculiar aspect of a selective process: this complementary structure is quite diverging from the genetic code. This analysis brings a strong argument against somatic theories, for the generation of diversity.

Amino Acid Sequence↗
PubMed2006

Metastatic breast cancer: an updating.

This article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined. DETECTION: Unlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with 'dynamic evaluation' of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations. PROGNOSIS AND THERAPY PREDICTORS: Disease-free interval (DFI) 24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents. THERAPY: Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called 'tailored' or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called 'oligometastatic' and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that 'biological' therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy.

Angiogenesis Inhibitors↗
PubMed2006

Language models based on Hebbian cell assemblies.

This paper demonstrates how associative neural networks as standard models for Hebbian cell assemblies can be extended to implement language processes in large-scale brain simulations. To this end the classical auto- and hetero-associative paradigms of attractor nets and synfire chains (SFCs) are combined and complemented by conditioned associations as a third principle which allows for the implementation of complex graph-like transition structures between assemblies. We show example simulations of a multiple area network for object-naming, which categorises objects in a visual hierarchy and generates different specific syntactic motor sequences ("words") in response. The formation of cell assemblies due to ongoing plasticity in a multiple area network for word learning is studied afterwards. Simulations show how assemblies can form by means of percolating activity across auditory and motor-related language areas, a process supported by rhythmic, synchronized propagating waves through the network. Simulations further reproduce differences in own EEG&MEG experiments between responses to word- versus non-word stimuli in human subjects.

Animals↗
PubMed2002

Functional domains of the rDNA promoter display a differential recognition in Leishmania.

A construct containing the RNA polymerase I promoter of Leishmania (L.) amazonensis, driving the expression of cloramphenicol acetyl transferase reporter gene, was better recognised by heterologous hosts species Leishmania (L.) major and Leishmania (L.) mexicana than by the homologous host L. (L.) amazonensis. The rDNA promoter domains responsible for recognition were functionally mapped. The core domain (-74 to +170) conferred a barely equal recognition on homologous or heterologous cells, slightly favouring to the later. Addition of the upstream domain (-196 to -74) repressed the expression in all cells tested. The third domain, consisting of repeated elements (upstream to -196 in L. (L.) amazonensis), enhanced by about 20 times the core activity of homologous species and by about 40 times the heterologous ones. Gel mobility shift patterns generated by the binding of core sequence of L. (L.) amazonensis to nuclear extracts of the Leishmania species suggested that the rDNA transcriptional machinery is a complex DNA-protein association particular for each species. A model is proposed to explain the mechanism and possible interactions of transcription machinery in the regulation of rDNA expression in phylogenically related organisms.

Animals↗
PubMed2003

Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5'-untranslated mRNA region.

Acetyl-CoA carboxylase 1 (ACC1) catalyzes the formation of malonyl-CoA, the C2 donor for de novo synthesis of long-chain fatty acids. We have identified 64 exons, including 7 alternatively spliced minor exons (1A, 1B, 1C, 3, 5A', 5A, and 5B) in human ACC1 gene ( approximately 330 kb). The gene is regulated by three promoters (PI, PII, and PIII), which are located upstream of exons 1, 2, and 5A, respectively. PI is a constitutive promoter and has no homology with the PI sequences of other mammalian ACC1. PII is regulated by various hormones. PIII is expressed in a tissue-specific manner. The presence of several alternatively spliced exons does not alter the translation of the 265-kDa ACC1 protein starting from an ATG present in exon 5. Translation of PIII transcripts from exon 5A generates a 259-kDa isoform in which the N-terminal 75 aa of 265-kDa ACC1 are replaced with a new sequence of 17 aa. Interestingly, the inclusion of exon 5B between 5A and 6 in PIII transcripts would yield a third 257-kDa isoform, which is translated from an ATG in exon 6. However, the presence of exon 5B in PI and PII transcripts leads to an in-frame stop codon that results in an ACC1-related 77-aa peptide. The presence of alternatively spliced exons and three isoforms of ACC1 could contribute to overall ACC1 activity either by influencing the mRNA stability and translational efficiency or by increasing the stability and specific activity of the ACC1 protein, respectively.

5' Untranslated Regions↗