RESUMO
We developed a genetic selection system based on nonsense suppression in Saccharomyces cerevisiae to identify mutations in proteins involved in transcription initiation by RNA polymerase III. A SUP4 tRNA(Tyr) internal promoter mutation (A53T61) that was unable to suppress ochre mutations in vivo and was incapable of binding TFIIIC in vitro was used as the target for selection of trans-acting compensatory mutations. We identified two such mutations in the same gene, which we named TAP1 (for transcription activation protein). The level of the SUP4A53T61 transcript was threefold higher in the tap1-1 mutant than in the wild type. The tap1-1 mutant strain was also temperature sensitive for growth. The thermosensitive character cosegregated with the restorer of suppression activity, as shown by meiotic linkage analysis and coreversion of the two traits. At 1 to 2 h after a shift to the restrictive temperature, RNA synthesis was strongly inhibited in the tap1-1 mutant, preceding any effect upon protein synthesis or growth. A marked decrease in tRNA and 5S rRNA synthesis was seen, and shortly after that, rRNA synthesis was inhibited. By complementation of the ts- growth defect, we cloned the wild-type TAP1 gene. It is essential for yeast growth. We show in the accompanying report (T. L. Aldrich, G. Di Segni, B. L. McConaughy, N. J. Keen, S. Whelen, and B. D. Hall, Mol. Cell. Biol. 13:3434-3444, 1993) that TAP1 is identical to RAT1, a yeast gene implicated in poly(A)+ RNA export and that the TAP1/RAT1 gene product has extensive sequence similarity to the protein encoded by another yeast gene (variously named DST2, KEM1, RAR5, SEP1, or XRN1) having exonuclease and DNA strand transfer activity (reviewed by Kearsey and Kipling [Trends Cell Biol. 1:110-112, 1991]).
Assuntos
Exorribonucleases , Proteínas Fúngicas/genética , Genes Fúngicos , Regiões Promotoras Genéticas , RNA de Transferência de Tirosina/genética , RNA de Transferência/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Transativadores/genética , Fatores de Transcrição TFIII , Fatores de Transcrição/metabolismo , Alelos , Ligação Competitiva , Clonagem Molecular , Cruzamentos Genéticos , DNA Fúngico/genética , DNA Fúngico/metabolismo , Proteínas Fúngicas/biossíntese , Mutação , Plasmídeos , RNA Fúngico/biossíntese , RNA Fúngico/genética , RNA Fúngico/metabolismo , Mapeamento por Restrição , Saccharomyces cerevisiae/crescimento & desenvolvimento , Supressão Genética , Transcrição GênicaRESUMO
Sequence data are presented for the Saccharomyces cerevisiae TAP1 gene and for a mutant allele, tap1-1, that activates transcription of the promoter-defective yeast SUP4 tRNA(Tyr) allele SUP4A53T61. The degree of in vivo activation of this allele by tap1-1 is strongly affected by the nature of the flanking DNA sequences at 5'-flanking DNA sequences as far away as 413 bp from the tRNA gene and by 3'-flanking sequences as well. We considered the possibility that this dependency is related to the nature of the chromatin assembled on these different flanking sequences. TAP1 encodes a protein 1,006 amino acids long. The tap1-1 mutation consists of a thymine-to-cytosine DNA change that changes amino acid 683 from tyrosine to histidine. Recently, Amberg et al. reported the cloning and sequencing of RAT1, a yeast gene identical to TAP1, by complementation of a mutant defect in poly(A) RNA export from the nucleus to the cytoplasm (D. C. Amberg, A. L. Goldstein, and C. N. Cole, Genes Dev. 6:1173-1189, 1992). The RAT1/TAP1 gene product has extensive sequence similarity to a yeast DNA strand transfer protein that is also a riboexonuclease (variously known as KEM1, XRN1, SEP1, DST2, or RAR5; reviewed by Kearsey and Kipling [Trends Cell Biol. 1:110-112, 1991]). The tap1-1 amino acid substitution affects a region of the protein in which KEM1 and TAP1 are highly similar in sequence.
Assuntos
DNA Fúngico/metabolismo , Exorribonucleases , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes Fúngicos , RNA de Transferência de Tirosina/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transativadores/genética , Transativadores/metabolismo , Transcrição Gênica , Sequência de Aminoácidos , Sequência de Bases , DNA Fúngico/genética , Expressão Gênica , Teste de Complementação Genética , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Plasmídeos , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Mapeamento por Restrição , Homologia de Sequência de AminoácidosRESUMO
BBR3464 is a new platinum-based drug non cross-resistant with cisplatin. To characterise the cellular basis of BBR3464 cytotoxicity as opposed to cisplatin, we performed a comparative study of the two drugs in cisplatin-resistant neuroblastoma and astrocytoma cells. In both model systems, BBR3464 proved to be more potent than cisplatin and was able to overcome cisplatin resistance. The higher potency exhibited by BBR3464 correlated with an increased cellular platinum accumulation and DNA-adduct formation. At equitoxic doses, BBR3464 induced apoptosis to a lesser extent than cisplatin and failed to overcome the decreased susceptibility to cisplatin-induced apoptosis in cisplatin-resistant cells. Cell cycle analysis showed a dose-dependent G2/M arrest by BBR3464. In astrocytoma cells, cisplatin treatment resulted in the upregulation of p53, p21 and bax, while only p21 induction was observed after BBR3464 treatment. In cisplatin-resistant cells, the reduced sensitivity to cisplatin paralleled a resistance to the induction of p53/p21 pathway by cisplatin, while the same doses of BBR3464 induced p21 to a similar extent in the resistant cells as in the parental cells. In conclusion, BBR3464 induces a cellular response that is different from cisplatin, supporting the view that the two drugs act through different mechanisms. Our data indicate that BBR3464 may be a promising agent in the treatment of tumours unresponsive to cisplatin and with a non-functional p53.
Assuntos
Antineoplásicos/uso terapêutico , Astrocitoma/tratamento farmacológico , Cisplatino/uso terapêutico , Neuroblastoma/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2 , Apoptose , Astrocitoma/metabolismo , Astrocitoma/patologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Proteínas Proto-Oncogênicas/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2 , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
In 1977 Costello described two unrelated children with poor postnatal growth, mental retardation, curly hair, coarse face of similar appearance, and nasal papillomata, suggesting the existence of a previously undescribed syndrome of uncertain familial nature [Costello, Aust Paediatr J 13: 114-118, 1977]. The existence of this syndrome as a separate entity was substantiated several years later by two additional reports by Der Kaloustian et al. [Am J Med Genet 43:678-685, 1991] and Martin and Jones [Am J Med Genet 41:346-349, 1991]. More recently Borochowitz et al. [Am J Med Genet 43:678-685, 1992] described a new "multiple congenital anomalies/mental retardation syndrome with facio-cutaneous-skeletal involvement." Whether this condition should be considered separately from the Costello syndrome is currently a matter of debate. We present three cases, two of whom are sibs, who support the identity of the two syndromes. Our aim is to better redefine the diagnostic criteria, describe the natural history, and confirm the genetic cause of the Costello syndrome, whose pattern of inheritance is most likely autosomal recessive.
Assuntos
Anormalidades Múltiplas , Nanismo , Face/anormalidades , Deficiência Intelectual , Anormalidades da Pele , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Cardiomiopatia Hipertrófica/genética , Nanismo/genética , Nanismo/patologia , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/patologia , Genes Recessivos , Cabelo/anormalidades , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Ceratodermia Palmar e Plantar , Masculino , Papiloma/genética , Fisiognomia , SíndromeRESUMO
PURPOSE: BBR 3464 is a promising new trinuclear platinum complex that has been shown to circumvent the resistance to cisplatin in a panel of tumor cell lines and xenografts with acquired or intrinsic resistance to cisplatin. The in vitro and in vivo antitumor activity of BBR 3464 was evaluated and compared with that of cisplatin in neuroblastoma. METHODS: In in vitro studies, the short- and long-term cytotoxicities, cell cycle perturbations, the ability to induce apoptosis, the intracellular platinum accumulation and DNA platination were evaluated in three neuroblastoma cell lines exposed to appropriate drug concentrations for 1 h. In in vivo studies, BBR 3464 was administered i.v. at doses of 0.30 and 0.35 mg/kg three times at intervals of 4 days (q4dx3), and cisplatin was administered i.v. according to two different schedules (at 2 and 4 mg/kg three times at intervals of 4 days and at 6 and 12 mg/kg as single doses). RESULTS: In a short-term growth inhibition assay, BBR 3464 was shown to be up to 100-fold more potent than cisplatin and it was even more potent in a clonogenic assay. The difference in the antitumor effect of BBR 3464 on the different cell lines was evident in both assays, while cisplatin exerted a comparable antitumor activity in all lines tested. Cell cycle analysis demonstrated a longer-lasting block in G2/M phase induced by BBR 3464 without the early S phase accumulation induced by cisplatin. The higher potency of BBR 3464 appeared to be unrelated to the induction of apoptosis, that was lower or at most comparable to cisplatin. Cellular platinum accumulation and platinum-DNA adduct formation following BBR 3464 exposure was higher than following cisplatin exposure. These differences may have resulted from a different mechanism of action and may explain the lack of cross-resistance with cisplatin. In xenografts of neuroblastoma, BBR 3464 was confirmed to be very potent as compared to cisplatin (MTD 0.35 mg/kg and 4 mg/kg for BBR 3464 and cisplatin, respectively). The efficacy of BBR 3464 was superior to that of cisplatin when both drugs were administered on a fractionated schedule (q4dx3), while BBR 3464 appeared equally active to 12 mg/kg cisplatin administered as a single dose. CONCLUSIONS: Our findings indicate that BBR 3464 has a definite antitumor effect in neuroblastoma lines and may be a candidate for early clinical trials in children with neuroblastoma.
Assuntos
Antineoplásicos/farmacologia , Neuroblastoma/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/metabolismo , Apoptose , Ciclo Celular/efeitos dos fármacos , Cisplatino/metabolismo , Cisplatino/uso terapêutico , DNA de Neoplasias/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Nus , Compostos Organoplatínicos/metabolismo , Transplante Heterólogo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Type II fucosidosis in an autosomal recessive disease. The paper presents a case of a patient with alpha-L-fucosidase of whom a skin specimen was examined under the electron microscope. Storage material was observed mainly in endothelial cells of blood capillaries and Schwann cells surrounding small peripheral nerves of papillary dermis. Within both cells two different kinds of inclusions were revealed: (1) clear vacuoles and (2) dense bodies with an internal structure prevalently lamellar. All these ultrastructural alterations were observed long before the appearance of clinically defined angiokeratoma at cutaneous level. Hence, they present the same alteration found in the absence of angiokeratoma in type I fucosidosis.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/patologia , Fucose/metabolismo , Pele/ultraestrutura , Angioceratoma/patologia , Pré-Escolar , Feminino , Humanos , Microscopia Eletrônica , Células de Schwann/ultraestrutura , Neoplasias Cutâneas/patologiaRESUMO
Anterior sacral meningocele has been reported to be associated with Marfan syndrome (MFS) in few cases, differently from dural ectasia appearing up to two thirds of affected patients. A new instance of this association is described in an 18-year-old man with Marfan syndrome, diagnosed upon MRI morphological evaluation which showed a huge cystic mass in the pelvic space. Surgical excision even if curative was not performed in consideration of a stationary picture after one year since diagnosis.
Assuntos
Síndrome de Marfan/patologia , Meningocele/patologia , Sacro/patologia , Adolescente , Dura-Máter/patologia , Seguimentos , Humanos , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Exame NeurológicoRESUMO
We describe our experience with 8 Italian patients having mucopolysaccharidosis type IV, diagnosed between 1 and 10 years of life, who presented odontoid hypoplasia causing cervical myelopathy. We discuss the possibility of cranio-cervical stabilization in order to reduce the neurological complications.
Assuntos
Mucopolissacaridose IV/patologia , Atrofia Muscular Espinal/patologia , Idade de Início , Criança , Pré-Escolar , Humanos , Lactente , Itália , Imageamento por Ressonância MagnéticaRESUMO
Previous studies have shown that there is a positive correlation between clinical expression of HIV-1 disease and deficits in the cognitive and neuropsychologic abilities in afflicted children. To date there are few studies regarding analysis of the cognitive and neuropsychologic development of HIV-positive, asymptomatic nonprogressor children (6-12 years of age) (long-survivors). The purpose of this study was to explore the differences in neuropsychologic development of asymptomatic HIV-positive school-age children compared with a seroreverted group. Evaluation was conducted in 8 children with asymptomatic or mild clinical signs of HIV infection compared with 8 seroreverted children. All tests were administered in three sessions by a trained specialist in neuropsychologic observation. The results of neuropsychologic testing suggested the presence of some learning disorders, as well as major memory and perception deficit. Most of the children tended to have levels of performance that were below normal values. The impairment could likely be the expression of a greater biologic vulnerability of HIV-positive children. Additional studies are necessary to define the risk factors and, hence, the protective factors that might support normal development of HIV-positive children.
Assuntos
Transtornos Cognitivos/etiologia , Soropositividade para HIV/complicações , HIV-1 , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Feminino , Soronegatividade para HIV , Soropositividade para HIV/diagnóstico , Humanos , Deficiências da Aprendizagem/etiologia , Masculino , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Prognóstico , Sensibilidade e EspecificidadeRESUMO
Autoimmune phenomena, especially occurrence of non organ-specific autoantibodies, are common in congenitally acquired HIV infection, mostly in the symptomatic stages of the disease. Anti-thyroid autoantibodies detected in adult patients represent the only type of organ-specific autoantibodies reported in HIV infection. As far as we know, occurrence of these autoantibodies has not been observed in HIV infected children. In this study thyroid biochemical pattern and possible occurrence of anti-thyroid autoantibodies were investigated in 40 vertically HIV infected, 18 seroreverted and 22 healthy children. 34% of HIV infected symptomatic children showed anti-thyroglobulin antibodies. Asymptomatic patients, seroreverted and healthy controls did not show any anti-thyroid antibodies at the time of the study. High Tg levels were observed in 38% of the 40 HIV infected patients and high TSH concentrations were found in 27.5% of the HIV children. High TSH values were more frequently observed in the infected children with moderate or severe immunocompromised status. Thyroxine binding globulin levels were high in 68% of the HIV children and in 22% of the seroreverted. The finding of anti-thyroid autoantibodies in congenital HIV infected children confirms the thyroid's involvement in HIV infection and provides more information about the wide spectrum of autoimmune phenomena observed in the infection.
Assuntos
Autoanticorpos/análise , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Glândula Tireoide/imunologia , Contagem de Linfócito CD4 , Pré-Escolar , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Humanos , Masculino , Valores de Referência , Tireoglobulina/sangue , Tireotropina/sangue , Tiroxina/sangue , Proteínas de Ligação a Tiroxina/análise , Tri-Iodotironina/sangueRESUMO
The Authors describe the case of a non-Hebrew Italian girl suffering from short-lasting fever episodes, associated with abdominal colic, since the age of 3. The occurrence of acute arthrosynovitis during the last episode, at 12 years of age, clinically confirms the diagnosis of familial mediterranean fever, as previously supposed. The increase in urinary coproporphyrins, with normal values of delta-aminolevulinic acid and porphobilinogen poses the problem of the differential diagnosis between hereditary coproporphyria and secondary coproporphinuria. The importance of this case lies in the presence of electroencephalographic alteration since the first years of life, suggesting a temporal epilepsy for which the patient was at length submitted to anti-epileptic treatment. Electroencephalographic alterations, of different type and uneasy interpretation, are described in the literature with a frequency which does not seem accidental. Renal biopsy does not show amyloid, nor the RMN reveals cerebral abnormalities. The anti-epileptic therapy being withdrawn, the patient was treated with daily administrations of colchicine (1 mg/die); 18 months after, she is disease free.
Assuntos
Eletroencefalografia , Febre Familiar do Mediterrâneo/diagnóstico , Fenômenos Bioquímicos , Bioquímica , Criança , Colchicina/uso terapêutico , Diagnóstico Diferencial , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/metabolismo , Feminino , HumanosRESUMO
The authors report their experience of a serial follow-up for congenital dysplasia of the hip (CDH). 699 babies born during a three-months period were examined on their first day of life, on the forth and at the age of 1 and 6 months. 2 dislocated hips, 222 clicking hips were discovered in the neonatal period. At the first month 1 dislocated hip and only 6 clicking hips were detected. At the sixth month all babies were normal with the exception of two clicking hips. X-ray examination confirmed clinical dislocation diagnosis and showed pathological signs (subluxation and acetabular dysplasia) also in normal and clicking hips. According to their results the authors suggest that clinical examination during the first 6 months of life and X-ray can decrease the incidence of late diagnosis of CDH.
Assuntos
Luxação Congênita de Quadril/diagnóstico , Feminino , Seguimentos , Humanos , Recém-Nascido , Apresentação no Trabalho de Parto , Masculino , GravidezAssuntos
Hospitais de Ensino , Neoplasias/diagnóstico , Pediatria/educação , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
A case control study on the association between maternal epilepsy, anticonvulsants use during pregnancy and birth defects was carried out in the Italian Multicentric Registry of Birth Defects (IPIMC). In the period 1980-1983, 7,607 malformed babies out of 439,717 total births (still + live) were registered. Fourty-one malformed babies with maternal epilepsy were identified (5.39 X 1,000). The overall relative risk of having a malformed baby among pregnant epileptic women was 1.87. Spina Bifida, Congenital Heart Defects, Clefts, Diaphragmatic Hernia and Trisomy 18 were more frequent than expected among babies with maternal epilepsy. The different therapeutic regimens were also tested to identify the possible independent teratogenic effect of anticonvulsants. A statistically significant association between Spina Bifida and Valproic Acid (odds ratio 22.7; Fisher p value = 0.0364) was observed: no other anticonvulsant tested showed any association with any type of malformation.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Anormalidades Congênitas/etiologia , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/epidemiologia , Aberrações Cromossômicas/induzido quimicamente , Aberrações Cromossômicas/etiologia , Transtornos Cromossômicos , Cromossomos Humanos Par 18 , Fenda Labial/induzido quimicamente , Fenda Labial/etiologia , Fissura Palatina/induzido quimicamente , Fissura Palatina/etiologia , Feminino , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/etiologia , Hérnia Diafragmática/induzido quimicamente , Hérnia Diafragmática/etiologia , Humanos , Recém-Nascido , Itália , Gravidez , Espinha Bífida Oculta/induzido quimicamente , Espinha Bífida Oculta/etiologia , Trissomia , Ácido Valproico/efeitos adversosRESUMO
A 16-year-old boy with Marfan's syndrome was admitted with progressive dyspnea due to a large spontaneous pneumothorax. Bullous pulmonary dysplasia was confirmed and pleural tube drainage did not affect the air leak. Complete recovery required surgical resection of the bulla responsible for the ongoing air leak. This case report highlights the issue of management for severe spontaneous pneumothorax in general, showing that the choice of treatment should not depend on the presence of pulmonary bullous dysplasia but on the clinical evaluation of the individual patient.
Assuntos
Vesícula/complicações , Pneumopatias/complicações , Síndrome de Marfan/complicações , Pneumotórax/etiologia , Adolescente , Humanos , Masculino , Pneumotórax/cirurgiaRESUMO
Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected.
Assuntos
Barbitúricos/uso terapêutico , Doenças do Prematuro/prevenção & controle , Icterícia Neonatal/prevenção & controle , Ensaios Clínicos como Assunto , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/tratamento farmacológico , MasculinoRESUMO
The authors describe a series of Haemophilus influenzae meningitis in childhood, obtained with a retrospective analysis of the cases of bacterial meningitis admitted to Isolamento Pediatrico department of "A. Gemelli" Polyclinic in Rome, from January 1, 1970 to December 31, 1994. Haemophilus influenzae resulted the second agent in frequency (first was Neisseria meningitidis). Main features were: no patient was older than 5 years, and most of them were less than 2 years old; clinical feature was aspecific in the first year of life, it was typical of bacterial meningitis in older children; blood culture and detection of bacterial antigens in cerebrospinal fluid (CSF) were useful for etiological diagnosis, supporting CSF culture; clinical course was characterized by many complications, but no case was lethal and incidence of sequelae at discharge was low; C reactive protein was effective as index of inflammation and as indicator of arising complications; chosen antibiotics were efficacious, but frequency of antibiotic resistance, especially to beta-lactams, was found to be increasing; results of dexamethasone therapy were not of univocal interpretation. The authors are in favour of spreading of vaccination against Haemophilus influenzae in Italy, too, in order to eradicate this disease, as experiences in other countries are successful, and of setting up of the combined vaccines, in order to increase parents' compliance to vaccinal practices.
Assuntos
Haemophilus influenzae/patogenicidade , Meningites Bacterianas/líquido cefalorraquidiano , Pré-Escolar , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Vacinas contra Influenza/uso terapêutico , Meningites Bacterianas/etiologia , Meningites Bacterianas/prevenção & controle , Estudos RetrospectivosRESUMO
Translation of globin mRNA in a micrococcal nuclease-treated reticulocyte lysate was studied in the presence of increasing amounts of Mengovirus RNA, under conditions in which the number of translation initiation events remains constant as judged by the transfer of label from N-formyl[35S]methionyl-tRNAf into protein. The translation of globin mRNA is progressively inhibited by low concentrations of Mengovirus RNA, free of detectable traces of double-stranded RNA, concomitant with the increasing synthesis of Mengovirus RNA-directed products. On a molar basis, Mengovirus RNA apparently competes about 35 times more effectively than globin mRNA for a critical component in translation. The competition is relieved by the addition of highly purified eukaryotic initiation factor 2 (eIF-2). Addition of eIF-2 does not stimulate overall protein synthesis, but shifts it in favor of globin synthesis. No stimulation of globin mRNA translation by eIF-2 is seen when Mengovirus RNA is absent. These experiments show that Mengovirus RNA competes, directly or indirectly, with globin mRNA for eIF-2. In direct binding experiments using isolated mRNA and eIF-2, Mengovirus RNA is shown to compete with globin mRNA for eIF-2 and to exhibit a 30-fold higher affinity for this factor. The binding of Mengovirus RNA to eIF-2 is much more resistant to increasing salt concentrations than is the binding of globin mRNA, again reflecting its high affinity. These results reveal a direct correlation between the ability of these mRNA species to compete in translation and their ability to bind to initiation factor eIF-2. They suggest that the affinity of a given mRNA species for eIF-2 is essential in determining its translation, relative to that of other mRNA species. Messenger RNA competition for eIF-2 may contribute significantly to the selective translation of viral RNA in infected cells.