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Biomedical subjects

C I González

Publications and source records attributed to C I González.

10 recordsLinked to original sources
PubMed2003

Characterization of reverse transcriptase activity of the L1Tc retroelement from Trypanosoma cruzi.

The recombinant protein RTL1Tc, encoded by the non-LTR (long terminal repeat) retrotransposon L1Tc from Trypanosoma cruzi, has been shown to have reverse transcriptase (RT) activity using poly(rA)/oligo(dT) and poly(rC)/oligo(dG) homopolymers as template/primers. The optimal RT activity was detected at a concentration of 5 mM Mg2+, pH 8 and between 28 and 37% degrees C. Site-directed mutagenesis in the RT catalytic site proved that substitution of aspartic acid 313 for isoleucine (RT D313IL1Tc) practically abolishes the RT activity of the RTL1Tc protein. RT-polymerase chain reaction assays revealed that the RTL1Tc protein has the ability to use both homologous and heterologous RNA templates. Also, it is shown that the RTL1Tc protein is capable of synthesizing complementary DNA molecules by consecutive switching of the oligo molecule, which the protein uses as a template. This template switching may be involved in the retroelement integration process.

Animals↗
PubMed2001

Nonsense-mediated mRNA decay in Saccharomyces cerevisiae.

Cell survival depends on the precise and correct production of polypeptides. Eukaryotic cells have evolved conserved proofreading mechanisms to get rid of incomplete and potentially deleterious proteins. The nonsense-mediated mRNA decay (NMD) pathway is an example of a surveillance mechanism that monitors premature translation termination and promotes degradation of aberrant transcripts that code for nonfunctional or even harmful proteins. In this review we will describe our current knowledge of the NMD pathway, analyzing primarily the results obtained from the yeast Saccharomyces cerevisiae, but establishing functional comparisons with those obtained in higher eukaryotes. Based on these observations, we present two related working models to explain how this surveillance pathway recognizes and selectively degrades aberrant mRNAs.

Codon, Nonsense↗
PubMed2000

The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay.

The nonsense-mediated mRNA decay (NMD) pathway monitors premature translation termination and degrades aberrant mRNAs. In yeast, it has been proposed that a surveillance complex searches 3' of a nonsense codon for a downstream sequence element (DSE) associated with RNA-binding proteins. An interaction between the complex and the DSE-binding protein(s) triggers NMD. Here we describe the identification and characterization of the Hrp1/Nab4 protein as a DSE-binding factor that activates NMD. Mutations in HRP1 stabilize nonsense-containing transcripts without affecting the decay of wild-type mRNAs. Hrp1p binds specifically to a DSE-containing RNA and interacts with Upf1p, a component of the surveillance complex. A mutation in HRP1 that stabilizes nonsense-containing mRNAs abolishes its affinity for the DSE and fails to interact with Upf1p. We present a model describing how Hrp1p marks a transcript for rapid decay.

Biological Transport↗
PubMed1999

Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover.

Eukaryotes have evolved conserved mechanisms to rid cells of faulty gene products that can interfere with cell function. mRNA surveillance is an example of a pathway that monitors the translation termination process and promotes degradation of transcripts harboring premature translation termination codons. Studies on the mechanism of mRNA surveillance in yeast and humans suggest a common mechanism where a "surveillance complex" monitors the translation process and determines whether translation termination has occurred at the correct position within the mRNA. A model will be presented that suggests that the surveillance complex assesses translation termination by monitoring the transition of an RNP as it is converted from a nuclear to a cytoplasmic form during the initial rounds of translation.

Animals↗
PubMed1999

Mutations in the MOF2/SUI1 gene affect both translation and nonsense-mediated mRNA decay.

Recent studies have demonstrated that cells have evolved elaborate mechanisms to rid themselves of aberrant proteins and transcripts. The nonsense-mediated mRNA decay pathway (NMD) is an example of a pathway that eliminates aberrant mRNAs. In yeast, a transcript is recognized as aberrant and is rapidly degraded if a specific sequence, called the DSE, is present 3' of a premature termination codon. Results presented here show that strains harboring the mof2-1, mof4-1, mof5-1, and mof8-1 alleles, previously demonstrated to increase the efficiency of programmed -1 ribosomal frameshifting, decrease the activity of the NMD pathway. The effect of the mof2-1 allele on NMD was characterized in more detail. Previous results demonstrated that the wild-type MOF2 gene is identical to the SUI1 gene. Studies on the mof2-1 allele of the SUI1 gene indicate that in addition to its role in recognition of the AUG codon during translation initiation and maintenance of the appropriate reading frame during translation elongation, the Mof2 protein plays a role in the NMD pathway. The Mof2p/Sui1 p is conserved throughout nature and the human homolog of the Mof2p/Sui1p functions in yeast cells to activate NMD. These results suggest that factors involved in NMD are general modulators that act in several aspects of translation and mRNA turnover.

Alleles↗
PubMed1998

Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA.

The nonsense-mediated mRNA decay (NMD) pathway functions by checking whether translation termination has occurred prematurely and subsequently degrading the aberrant mRNAs. In Saccharomyces cerevisiae, it has been proposed that a surveillance complex scans 3' of the premature termination codon and searches for the downstream element (DSE), whose recognition by the complex identifies the transcript as aberrant and promotes its rapid decay. The results presented here suggest that translation termination is important for assembly of the surveillance complex. Neither the activity of the initiation ternary complex after premature translation termination has occurred nor the elongation phase of translation are essential for the activity of the NMD pathway. Once assembled, the surveillance complex is active for searching and recognizing a DSE for approximately 200 nt 3' of the stop codon. We have also identified a stabilizer sequence (STE) in the GCN4 leader region that inactivates the NMD pathway. Inactivation of the NMD pathway, as a consequence of either the DSE being too far from a stop codon or the presence of the STE, can be circumvented by inserting sequences containing a new translation initiation/termination cycle immediately 5' of the DSE. Further, the results indicate that the STE functions in the context of the GCN4 transcript to inactivate the NMD pathway.

Codon↗
PubMed1998

[Primitive neuroectodermal tumors: difficult tumors versus modern oncology].

INTRODUCTION: Primitive peripheral neuroectodermal tumours (PNET) are rare masses and form part of the group of round small cell tumours which include a wide range of highly aggressive neoplasias such as Ewing's sarcoma, neuroblastoma, lymphoma and rhabdomyosarcoma. PNET present the same cell line as the tumours presented by F. Askin in 1979, both located in the thoracic-pulmonary region. MATERIAL AND METHODS: Of the last 26 thoracic neuroblastomas and 11 mediastinal-thoracic sarcomas treated at our centre, we observed 5 PNET in children with a mean age of 12 years (range: 9-14 years). These patients presented a thoracic mass infiltrating sternum, clavicle, supraspinal muscle or, in two cases, a left lateral or paravertebral intrathoracic mass. The time elapsed between clinical observation and diagnosis was 6 weeks. Diagnosis was established by chest X-Ray, CT, bone scintigraphy, immunocytochemistry and cytology. Aggressive local treatment associated with stage IV SIOP chemotherapy for rhabdomyosarcoma was applied in all cases to prevent metastasis. RESULTS: Of the five PNET treated, one 16-year-old patient died (4 y 5 m post-diagnosis) from bone marrow infiltration which had evolved badly from the beginning. The remaining patients are disease-free. One patient who did not undergo surgery relapsed 1 year and the half after completing chemotherapy. He then underwent resection of the cranial portion of the sternum and substitution with iliac graft from the tissue bank. CONCLUSION: PNET manifest clearly some of the characteristics of current paediatric oncology. These tumours are easily misdiagnosed and at present may be differentiated by new diagnostic methods (immunohistochemistry, cytogenetics, hybridomas, molecular genetics), with the aim of selecting the most adequate treatment and consequently improving the prognosis of these aggressive embryonary tumours.

Adolescent↗
PubMed1997

Reverse transcriptase-like activity in Trypanosoma cruzi.

The use of specific synthetic RNA homopolymers as templates and short oligonucleotides as primers has allowed evidence of the existence of a reverse transcriptase-like activity in Trypanosoma cruzi, to be revealed. The RNA:DNA products derived from this reaction are of approximately 110 nucleotides in length. The enzyme has greater affinity for poly(rA)/ oligo(dT) templates than for poly(rC)/oligo(dG) having a 20 mM Mg+2 ion requirement. The detected reverse transcriptase-like activity is not affected by aphidicolin and ddTTP but is inhibited by actinomycin D. novobiocin, rifamycin SV and AZT.

Animals↗
PubMed1989

Current findings in the pathological evaluation of breast reduction specimens.

A study of the histopathologic findings in the specimens of 100 consecutive cases of reduction mammoplasty was performed. The current classification of premalignant breast changes using the presence or absence of atypia in specimens with epithelial hyperplasia was employed. Of the group studied only 1% showed atypical ductal hyperplasia and no cases of lobular carcinoma in situ or ductal carcinoma in situ were found. Fifty percent of the specimens showed simply fibrosis of the stroma dominating the gross and microscopic picture. The other pathological findings in descending order of frequency were cysts (30%) epithelial hyperplasia without atypia (6%), adenosis (5%) and apocrine metaplasia (5%).

Adolescent↗