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A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans.

Highly efficient cap-independent translation initiation at the 5'-proximal AUG is facilitated by the 3' translation enhancer sequence (3'TE) located near the 3' end of barley yellow dwarf virus (BYDV) genomic RNA. The role of the 3'TE in regulating viral translation was examined. The 3'TE is required for translation and thus replication of the genomic RNA that lacks a 5' cap (Allen et al., 1999, Virology253:139-144). Here we show that the 3'TE also mediates translation of uncapped viral subgenomic mRNAs (sgRNA1 and sgRNA2). A 109-nt viral sequence is sufficient for 3'TE activity in vitro, but additional viral sequence is necessary for cap-independent translation in vivo. The 5' extremity of the sequence required in the 3' untranslated region (UTR) for cap-independent translation in vivo coincides with the 5' end of sgRNA2. Thus, sgRNA2 has the 3'TE in its 5' UTR. Competition studies using physiological ratios of viral RNAs showed that, in trans, the 109-nt 3'TE alone, or in the context of 869-nt sgRNA2, inhibited translation of genomic RNA much more than it inhibited translation of sgRNA1. The divergent 5' UTRs of genomic RNA and sgRNA1 contribute to this differential susceptibility to inhibition. We propose that sgRNA2 serves as a novel regulatory RNA to carry out the switch from early to late gene expression. Thus, this new mechanism for temporal control of translation control involves a sequence that stimulates translation in cis and acts in trans to selectively inhibit translation of viral mRNA.

3' Untranslated Regions↗

The iron regulatory region of ferritin mRNA is also a positive control element for iron-independent translation.

The iron regulatory element (IRE) in the 5'-untranslated region of ferritin mRNA interacts with a specific regulator protein (P-90, IRE-BP, or FRP) to block translation. High cellular iron changes the IRE/P-90 interaction to relax the translational block and allow polyribosome formation. We now show that the IRE and base-paired flanking regions also enhance translation in the absence of P-90, explaining the high translational efficiency of deregulated ferritin mRNA observed previously. The effect of the IRE on translational efficiency was examined by comparing four sets of mRNAs: (1) +/- IRE in animal (frog) ferritin, regulated translationally by iron in vivo; (2) +/- animal IRE fused with plant (soybean) ferritin, regulated transcriptionally by iron in vivo; (3) repositioned IRE in animal ferritin; (4) mutated IRE in animal ferritin with G16A substitution, which decreases P-90 binding (negative control). The IRE region increased translational efficiency of both the animal ferritin and the heterologous IRE/soybean ferritin fusion mRNAs; the effect was observed in cell-free translation systems from either plants (wheat germ) or animals (rabbit reticulocyte). Repositioning the IRE further from the 5' cap eliminated positive control of translation. The single base mutation had no effect, indicating that positive and negative translational control involves different sections of the IRE region. Thus, the IRE region in ferritin mRNA encodes both positive translational control and, when combined with the regulator protein P-90, negative translational control.

Animals↗

Determinants of the translational mobility of a small solute in cell cytoplasm.

The purposes of this study were: (a) to measure the translational mobility of a small solute in cell cytoplasm; (b) to define quantitatively the factors that determine solute translation; and (c) to compare and contrast solute rotation and translation. A small fluorescent probe, 2,7-bis-(2-carboxyethyl)-5-(and 6-)-carboxyfluorescein (BCECF), was introduced into the cytoplasm of Swiss 3T3 fibroblasts. BCECF translation was measured by fluorescence recovery after photo-bleaching; rotation was measured by Fourier transform polarization microscopy. Diffusion coefficients relative to those in water (D/D0) were determined by comparing mobility in cytoplasm with mobility in standard solutions of known viscosity. At isosmotic cell volume, the relative diffusion coefficients for BCECF translation and rotation in cytoplasm were 0.27 +/- 0.01 (SEM, n = 24, 23 degrees C) and 0.78 +/- 0.03 (n = 4), respectively. As cell volume increased from 0.33 to 2 times isosmotic volume, the relative translational diffusion coefficient increased from 0.047 to 0.32, while the relative rotational diffusion coefficient remained constant. The factors determining BCECF translation were evaluated by comparing rotation and translation in cytoplasm, and in artificial solutions containing dextrans (mobile barriers) and agarose gels (immobile barriers). It was concluded that the hindrance of BCECF translation in cytoplasm could be quantitatively attributed to three independent factors: (a) fluid-phase cytoplasmic viscosity is 28% greater than the viscosity of water (factor 1 = 0.78); (b) 19% of BCECF is transiently bound to intracellular components of low mobility (factor 2 = 0.81); and most importantly, (c) translation of unbound BCECF is hindered 2.5-fold by collisions with cell solids comprising 13% of isosmotic cell volume (factor 3 = 0.40). The product of the 3 factors is 0.25 +/- 0.03, in good agreement with the measured D/D0 of 0.27 +/- 0.01. These results provide the first measurement of the translational mobility of a small solute in cell cytoplasm and define quantitatively the factors that slow solute translation.

3T3 Cells↗

Translation of the psbA mRNA of Chlamydomonas reinhardtii requires a structured RNA element contained within the 5' untranslated region.

Translational regulation is a key modulator of gene expression in chloroplasts of higher plants and algae. Genetic analysis has shown that translation of chloroplast mRNAs requires nuclear-encoded factors that interact with chloroplastic mRNAs in a message-specific manner. Using site-specific mutations of the chloroplastic psbA mRNA, we show that RNA elements contained within the 5' untranslated region of the mRNA are required for translation. One of these elements is a Shine-Dalgarno consensus sequence, which is necessary for ribosome association and psbA translation. A second element required for high levels of psbA translation is located adjacent to and upstream of the Shine-Dalgarno sequence, and maps to the location on the RNA previously identified as the site of message-specific protein binding. This second element appears to act as a translational attenuator that must be overcome to activate translation. Mutations that affect the secondary structure of these RNA elements greatly reduce the level of psbA translation, suggesting that secondary structure of these RNA elements plays a role in psbA translation. These data suggest a mechanism for translational activation of the chloroplast psbA mRNA in which an RNA element containing the ribosome-binding site is bound by message-specific RNA binding proteins allowing for increased ribosome association and translation initiation. These elements may be involved in the light-regulated translation of the psbA mRNA.

Animals↗

Expression of muscle-specific proteins is necessary to regulate translation of the mRNA for a 40-kDa housekeeping polypeptide in rat L6 cells.

Translation of the mRNA for a housekeeping polypeptide of 40 kDa (P40) was found to be regulated under a variety of conditions in rat L6 cells. This mRNA was translated in the proliferating myoblasts but not in the non-proliferating myotubes. A number of chemicals, such as dimethyl sulfoxide, sodium butyrate and aphidicolin, were used to prevent expression of muscle-specific genes in mitogen-poor differentiation medium. In the absence of any detectable accumulation of muscle-specific alpha-actin mRNA, the P40 mRNA remained in the translated state. A fourth chemical, EGTA, a known inhibitor of fusion of muscle cells, blocked translation of muscle-specific actin and tropomyosin mRNAs. On the other hand, it showed no effect on the translation of P40 mRNA. Addition of Ca2+ to the EGTA-treated cultures, however, almost completely reversed the block of translation of actin tropomyosin mRNAs within four days. Concomitant to Ca2+ reversal of the translational block of muscle mRNAs, P40 mRNA entered the non-translated state. An inverse relationship, therefore, was observed between the translation of housekeeping P40 mRNA and muscle-specific mRNAs. The ability to mimic in vivo regulation of P40 mRNA translation was examined in mRNA-dependent micrococcal-nuclease-treated homologous cell-free extracts. The extracts from myoblasts and myotubes were able to translate P40 mRNA. Furthermore, ribosomes of both myoblast and myotube extracts containing endogenous mRNAs were also able to bind to P40 and actin mRNAs. Myotube extract, however, showed a lower binding ability to P40 mRNA than to the actin mRNA. The ability of ribosomes of myotube extract to bind P40 mRNA was somewhat enhanced by addition of proteins derived from washing these ribosomes with a high-ionic-strength buffer. In order to elucidate the role of interaction between mRNA and proteins in translational control of P40 mRNA, the polypeptide complements of polysomal and free P40 mRNA-protein (mRNP) complexes were also examined. Hybrid selection of polysomal and free P40 mRNP complexes followed the covalent joining of the RNA and protein moieties of mRNP complexes by ultraviolet irradiation of rat L6 cells. Analysis of buoyant densities of these complexes showed that free P40 mRNP had slightly less protein than polysomal P40 mRNP. Furthermore, analysis of the polypeptide complements of both free and polysomal P40 mRNP complexes showed that they were composed of identical polypeptides. The only detectable difference between the polypeptide complements of these complexes was that two polypeptides of 72 kDa and 55 kDa were more abundant in the polysomal P40 mRNP than free P40 mRNP.

Actins↗

Mutational alterations of translational coupling in the L11 ribosomal protein operon of Escherichia coli.

The L11 operon in Escherichia coli consists of the genes coding for ribosomal proteins L11 and L1. It is known that translation of L1 does not take place unless the preceding L11 cistron is translated, that is, the two cistrons are translationally coupled, and this is the basis of coregulation of the translation of the two cistrons by a single repressor, L1. Several mutational analyses were carried out to define the region responsible for coupling L1 translation with L11 translation. First, by introducing several amber mutations into the L11 gene by a site-directed mutagenesis technique, it was shown that translation by ribosomes down to a position 21 nucleotides upstream, but not to a position 45 nucleotides upstream, from the end of the L11 cistron allowed the initiation of L11 translation. Second, deletion analysis indicated that a region located 23 to 20 nucleotides from the end of the L11 gene was involved in preventing independent initiation from L1 translation. Third, five different mutations obtained by screening for activation of the masked L1 initiation site were found to be clustered in a small region immediately upstream from the Shine-Dalgarno sequence of L1, and all of them were G-to-A transitions. These results, together with some additional experiments with oligonucleotide-directed mutagenesis, defined the region involved in the coupling and suggest that some special feature of this region, probably different from simple masking of the initiation site by base pairing, is responsible for translational coupling. The present results also suggest that there might be specific differences in the primary nucleotide sequence that distinguish independent translational initiation sites from translationally coupled (i.e., masked) initiation sites.

Bacterial Proteins↗

Modifications of the 5' cap of mRNAs during Xenopus oocyte maturation: independence from changes in poly(A) length and impact on translation.

The translation of specific maternal mRNAs is regulated during early development. For some mRNAs, an increase in translational activity is correlated with cytoplasmic extension of their poly(A) tails; for others, translational inactivation is correlated with removal of their poly(A) tails. Recent results in several systems suggest that events at the 3' end of the mRNA can affect the state of the 5' cap structure, m7G(5')ppp(5')G. We focus here on the potential role of cap modifications on translation during early development and on the question of whether any such modifications are dependent on cytoplasmic poly(A) addition or removal. To do so, we injected synthetic RNAs into Xenopus oocytes and examined their cap structures and translational activities during meiotic maturation. We draw four main conclusions. First, the activity of a cytoplasmic guanine-7-methyltransferase increases during oocyte maturation and stimulates translation of an injected mRNA bearing a nonmethylated GpppG cap. The importance of the cap for translation in oocytes is corroborated by the sensitivity of protein synthesis to cap analogs and by the inefficient translation of mRNAs bearing nonphysiologically capped 5' termini. Second, deadenylation during oocyte maturation does not cause decapping, in contrast to deadenylation-triggered decapping in Saccharomyces cerevisiae. Third, the poly(A) tail and the N-7 methyl group of the cap stimulate translation synergistically during oocyte maturation. Fourth, cap ribose methylation of certain mRNAs is very inefficient and is not required for their translational recruitment by poly(A). These results demonstrate that polyadenylation can cause translational recruitment independent of ribose methylation. We propose that polyadenylation enhances translation through at least two mechanisms that are distinguished by their dependence on ribose modification.

Animals↗

Yeast Lsm1p-7p/Pat1p deadenylation-dependent mRNA-decapping factors are required for brome mosaic virus genomic RNA translation.

Previously, we used the ability of the higher eukaryotic positive-strand RNA virus brome mosaic virus (BMV) to replicate in yeast to show that the yeast LSM1 gene is required for recruiting BMV RNA from translation to replication. Here we extend this observation to show that Lsm1p and other components of the Lsm1p-Lsm7p/Pat1p deadenylation-dependent mRNA decapping complex were also required for translating BMV RNAs. Inhibition of BMV RNA translation was selective, with no effect on general cellular translation. We show that viral genomic RNAs suitable for RNA replication were already distinguished from nonreplication templates at translation, well before RNA recruitment to replication. Among mRNA turnover pathways, only factors specific for deadenylated mRNA decapping were required for BMV RNA translation. Dependence on these factors was not only a consequence of the nonpolyadenylated nature of BMV RNAs but also involved the combined effects of the viral 5' and 3' noncoding regions and 2a polymerase open reading frame. High-resolution sucrose density gradient analysis showed that, while mutating factors in the Lsm1p-7p/Pat1p complex completely inhibited viral RNA translation, the levels of viral RNA associated with ribosomes were only slightly reduced in mutant yeast. This polysome association was further verified by using a conditional allele of essential translation initiation factor PRT1, which markedly decreased polysome association of viral genomic RNA in the presence or absence of an LSM7 mutation. Together, these results show that a defective Lsm1p-7p/Pat1p complex inhibits BMV RNA translation primarily by stalling or slowing the elongation of ribosomes along the viral open reading frame. Thus, factors in the Lsm1p-7p/Pat1p complex function not only in mRNA decapping but also in translation, and both translation and recruitment of BMV RNAs to viral RNA replication are regulated by a cell pathway that transfers mRNAs from translation to degradation.

Blotting, Northern↗

Glenohumeral translation in the asymptomatic athlete's shoulder and its relationship to other clinically measurable anthropometric variables.

To determine the degree of shoulder translation in uninjured athletes, we examined 76 Division I collegiate athletes (44 women and 32 men) for passive range of motion in both shoulders and for knee and elbow hyperextension. Translation was based on a scale of 0 to 3+. Shoulders with symptoms of pain or a history of instability or dislocation were excluded from this study. Forty-six shoulders had 0 anterior translation, 75 had 1+, and 31 had 2+. Thirteen shoulders had 0 posterior translation, 56 had 1+, and 83 had 2+. Thirty-eight shoulders had 0 inferior translation, 105 had 1+, and 9 had 2+. No shoulder had translation of 3+ in any direction. Twenty-four athletes, 12 men and 12 women, had translational asymmetry of a minimum of one grade in at least one direction. No shoulder was asymmetric in all three directions. There was a significant correlation between dominant hand and increased translation; 19 of 24 athletes with asymmetric shoulders had greater translation in the nondominant extremity. There was no relationship between translation and range of motion, knee or elbow hyperextension, thumb-to-forearm distance, or years spent in sports participation. Asymmetry of shoulder translation may exist in the normal shoulder. This review shows that up to 2+ translation in any direction cannot be considered abnormal.

Elbow Joint↗

Preferential translation of cold-shock mRNAs during cold adaptation.

Upon temperature downshift below the lower threshold of balanced growth (approximately 20 degrees C), the Escherichia coli translational apparatus undergoes modifications allowing the selective translation of the transcripts of cold shock-induced genes, while bulk protein synthesis is drastically reduced. Here we were able to reproduce this translational bias in E. coli cell-free extracts prepared at various times during cold adaptation which were found to display different capacities to translate different types of mRNAs as a function of temperature. Several causes were found to contribute to the cold-shock translational bias: Cold-shock mRNAs contain cis-elements, making them intrinsically more prone to being translated in the cold, and they are selective targets for trans-acting factors present in increased amounts in the translational apparatus of cold-shocked cells. CspA was found to be among these trans-acting factors. In addition to inducing a higher level of CspA, cold shock was found to cause a strong (two- to threefold) stoichiometric imbalance of the ratio between initiation factors (IF1, IF2, IF3) and ribosomes without altering the stoichiometric ratio between the factors themselves. The most important sources of cold-shock translational bias is IF3, which strongly and selectively favors translation of cold-shock mRNAs in the cold. IF1 and the RNA chaperone CspA, which stimulate translation preferentially in the cold without mRNA selectivity, can also contribute to the translational bias. Finally, in contrast to a previous claim, translation of cold-shock cspA mRNA in the cold was found to be as sensitive as that of a non-cold-shock mRNA to both chloramphenicol and kanamycin inhibition.

Anti-Bacterial Agents↗

Arthroscopic anteroinferior suture plication resulting in decreased glenohumeral translation and external rotation. Study of a cadaver model.

BACKGROUND: The consequences of arthroscopic plication for the treatment of anterior shoulder instability are unknown. The purpose of this study was to evaluate the effects of arthroscopic plication on glenohumeral translation, the rotational range of motion, and the positions of the glenohumeral center of rotation. METHODS: Six cadaver shoulders were tested in the intact state, after simulation of anterior instability by anterior capsular stretching, after creation of arthroscopic portals, and following a 10-mm anteroinferior arthroscopic suture plication. Capsulolabral build-up was measured to quantify the increase after plication. RESULTS: Stretching resulted in a significant increase, compared with the intact state, in external rotation (mean increase, 23.2 degrees [14.3%]; p < 0.001) but not in glenohumeral translation (mean increase, 0.8 mm [7.4%] under a 20-N translational load; p = 0.06). After plication, external rotation decreased significantly (by 12.6 degrees [6.7%], p = 0.003) compared with that following the stretching. After plication, the glenohumeral center of rotation was significantly shifted posteriorly at 60 degrees , 90 degrees , and 120 degrees of external rotation and inferiorly at 90 degrees and 120 degrees . Plication also resulted in significant decreases in anterior translation (mean decrease, 61.1% under a 15-N translational load and 49.8% under a 20-N translational load; p < 0.001), posterior translation (mean decrease, 11.4% under a 15-N translational load and 13.1% under a 20-N translational load; p = 0.002 and p < 0.001, respectively), and inferior translation (mean decrease, 3.2% under a 20-N load; p = 0.04). The height of the capsulolabral "bumper" increased from 2.9 mm in the intact state to 6.4 mm following plication (p = 0.001). CONCLUSIONS: Arthroscopic anteroinferior plication effectively reduces anterior translation and external rotation. Capsulolabral buildup may help limit anterior translation without affecting rotation. Plication resulted in a shift of the glenohumeral center of rotation posteriorly and inferiorly.

Aged↗

Rapid translation of quality of life measures for international clinical trials: avoiding errors in the minimalist approach.

There is a growing demand for tools to assess outcomes multinationally for use in international clinical trials. This has been accompanied by the need to produce valid and reliable questionnaires in a multiplicity of languages within a short time frame. We present an eight-step protocol for rapidly translating a quality of life (QOL) questionnaire into multiple languages, and demonstrate the protocol's utility and effectiveness by evaluating the translations for reliability and validity. The rapid translation protocol represents a minimalist approach to QOL questionnaire translation. Although this minimalist approach is not considered a recommended methodology, it may represent a feasible mechanism for questionnaire translation under certain circumstances. Most of the steps were completed in the USA, including a translation and back-translation by bilingual translators who were native speakers in the target-language, a test-retest of the translated instrument on five bilingual respondents to establish language and cultural equivalence and review of the translation by and editorial review board. The translated instrument was performance tested in the target language country on a pilot population of patients to determine its reliability and validity. Based on the findings, the instrument was further refined for use in the clinical trial.

Adult↗

Translation and cultural adaptation of Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) with application to survivors of childhood cancer in Brazil.

INTRODUCTION: There are few publications reporting health-related quality of life (HRQL) in developing nations. Most instruments measuring HRQL have been developed in English-speaking countries. These instruments need to be culturally adapted for use in non-English-speaking countries. The HUI2 and HUI3 are generic, preference-based systems for describing health status and HRQL. Developed in Canada, the systems have been translated into more than a dozen languages and used worldwide in hundreds of studies of clinical and general populations. METHODS: The Brazilian-Portuguese translation of the HUI systems was supervised by senior HUInc staff having experience with both the HUI systems and translations. The process included two independent forward translations of the multi-attribute health status classification systems and related questionnaires, consensus between translators on a forward translation, back-translation by two independent translators of the forward translation, and review of the back-translations by original developers of the HUI. The final questionnaires were tested by surveying a sample of convenience of 50 patients recruited at the Centro de Tratamento e Pesquisa-Hospital do Cancer in São Paulo, Brazil. RESULTS: Fifty patients were enrolled in the study. No assessor, patient or nurse or physician, reported problems answering the HUI questionnaires. No significant differences were found in mean overall HUI2 or HUI3 utility scores among types of assessors. Variability in scores are similar to those from other studies in Latin America and Canada. CONCLUSION: Test results provide preliminary evidence that the Brazilian-Portuguese translation is acceptable, understandable, reliable and valid for assessing health-status and HRQL among survivors of cancer in childhood in Brazil.

Adult↗

Translating the Short-Form Headache Impact Test (HIT-6) in 27 countries: methodological and conceptual issues.

The process of translating the Short-Form Headache Impact Test (HIT-6) in 27 countries and the comparability of the content of the translations is discussed. HIT-6 translations were developed using a standard forward-backward translation process, including a cognitive debriefing step and international harmonization of the translations. Prior to translating the HIT-6, modifications were made to the English-language source form, to improve translation equivalence. In general, the HIT-6 was not difficult to translate. The most difficult items included colloquial expressions such as 'fed up' and words whose intended meaning changed in translation such as 'school' or 'lie down.' Subjects generally found the HIT-6 translations to be clear and relevant. The translation process resulted in questionnaires that are both culturally appropriate and comparable in content.

Headache↗

Heat-shock protein synthesis in Chlamydomonas reinhardi. Translational control at the level of initiation of a poly(A)-rich-RNA coded 22-KDa protein in a cell-free system.

The effect of temperature on the in vitro translation of control and heat-shock poly(A)-rich RNA, obtained from Chlamydomonas reinhardi cells, incubated for 2 h at 25 degrees C respectively, was studied using the wheat-germ translation system. Incubation of the cells at 42 degrees C induces the synthesis of RNAs coding for several heat-shock proteins, including a 22-kDa major polypeptide as well as several proteins of 45-94 kDa, as demonstrated by run-off translation of polyribosomes isolated from intact cells. However, the high-molecular-mass heat-shock proteins are poorly translated in the wheat-germ system. The poly(A)-rich RNA coding for the 22-kDa heat-induced polypeptide has an apparent sedimentation coefficient higher than that expected from the molecular mass of its translation product, and was preferentially translated in vitro at temperatures above 31 degrees C as compared with pre-existing RNAs. Raising the temperature of translation, slightly inhibited (10%) the runoff translation of polyribosomes isolated from intact cells. However, when initiation was carried out in vitro for a short time at increasing temperatures and translation continued at 25 degrees C in the presence of aurintricarboxylic acid, the 22-kDa heat-shock polypeptides was preferentially translated. Aurintricarboxylic acid did not significantly inhibit incorporation of [35S]methionine when added to polyribosomes isolated from control or heat-shocked cells. From the above data we conclude that the translation of the 22-kDa heat-shock protein is controlled in vitro at the initiation level.

Cell-Free System↗

Novel spanish translators for acute care nurses and physicians: usefulness and effect on practitioners' stress.

BACKGROUND: Language barriers are significant impediments to providing quality health care, and increased stress levels among nurses and physicians are associated with these barriers. However, little evidence supports the usefulness of a translation tool specific to health care. OBJECTIVES: To evaluate the effectiveness of a novel English-Spanish translator designed specifically for nurses and physicians. The hypothesis was that the translator would be useful and that use of the translator would decrease stress levels among nurses and physicians caring for Spanish-speaking patients. METHODS: Novel English-Spanish translators were developed entirely on the basis of input from critical care nurses and physicians. After 7 months of use, users completed surveys. Usefulness of the translator and stress levels among users were reported. RESULTS: A total of 60% of nurses (n=32) and 71% (n=25) of physicians responded to the survey. A total of 96% of physicians and 97% of nurses considered the language barrier an impediment to delivering quality care. Nurses reported significantly more stress reduction than did physicians (P=.01). Most nurses and physicians had used the translator during the survey period. Overall, 91% of nurses and 72% of physicians found that the translator met their needs at the bedside some, most, or all of the time. All nurses thought that they most likely would use the translator in the future. CONCLUSIONS: The translator was useful for most critical care nurses and physicians surveyed. Health care providers, especially nurses, experienced decreased stress levels when they used the translator.

Communication Barriers↗

TWENTY-FIVE YEARS OF TRANSLATING SERVICE AT NIH.

The growth of the Translating Unit of the National Institutes of Health Library, founded in 1938, was slow until 1950, when seventeen translators and clerical assistants comprised its staff. Today eleven staff members translate, type, and distribute translations from eighteen European languages. Contract service is arranged for those languages for which the Unit has little or no competency. Three recent innovations have improved the translating service: (1) production standards, (2) fee for service, and (3) microfilmed translations. A monthly bulletin, Recent Translations, a Selected List, includes those articles translated by the Translating Unit of the NIH Library. An author index to all translations cited in the Selected List is now available upon request.

Computer Systems↗

Expression profile of eukaryotic translation factors in human cancer tissues and cell lines.

Several studies have demonstrated the overexpression of certain eukaryotic translation factors in human cancer cell lines and in malignant tissues. In this study, with human cancer cell lines derived from lungs, breast, prostate, and skin, we have examined the expression profile of 36 translation factors consisting of 27 initiation factors, 8 elongation factors, and 1 termination factor. Translation initiation factors 2C2 and 4E1 and translation elongation factors 1A2 and 1delta were found overexpressed (2- to 2000-fold) in many of the cancer cell lines compared to their corresponding normal cell lines. Among the translation factors analyzed, translation elongation factor 1A2 exhibited the most significant alteration in expression: 10- to 2000-fold overexpression was noticed in nine out of ten cancer cell lines analyzed. Whether the overexpression of translation elongation factor 1A2 can be used as a potential tumor marker was tested with the cancer profiling array (BD Biosciences, Palo Alto, CA) consisting of 241 paired cDNA samples generated from 13 different cancer/noncancer tissue types. Overexpression of translation elongation factor 1A2 was noticed in several tumor tissue samples, most notably in the human colon cancer samples which exhibited at least a twofold overexpression among 35% of the samples analyzed. Besides colon, tumor samples derived from lungs, kidney, rectum, and ovary also exhibited more than a twofold overexpression of translation elongation factor 1A2 in at least 20% of the samples analyzed. These results indicate that human carcinogenesis is often associated with alterations in the expression of various translation factors especially the overexpression of eukaryotic translation elongation factor 1A2.

Breast Neoplasms↗