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Biomedical subjects

G Dreyfuss

Publications and source records attributed to G Dreyfuss.

At least 73 records · Page 4Linked to original sources
PubMed2000

The survival motor neuron protein of Schizosacharomyces pombe. Conservation of survival motor neuron interaction domains in divergent organisms.

Spinal muscular atrophy is a common often lethal neurodegenerative disease resulting from deletions or mutations in the survival motor neuron gene (SMN). SMN is ubiquitously expressed in metazoan cells and plays a role in small nuclear ribonucleoprotein assembly and pre-mRNA splicing. Here we characterize the Schizosacharomyces pombe orthologue of SMN (yeast SMN (ySMN)). We report that the ySMN protein is essential for viability and localizes in both the cytoplasm and the nucleus. Like human SMN, we show that ySMN can oligomerize. Remarkably, ySMN interacts directly with human SMN and Sm proteins. The highly conserved carboxyl-terminal domain of ySMN is necessary for the evolutionarily conserved interactions of SMN and required for cell viability. We also demonstrate that the conserved amino-terminal region of ySMN is not required for SMN and Sm binding but is critical for the housekeeping function of SMN.

Amino Acid Sequence↗
PubMed2000

Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli.

The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3. The tight interaction of Gemin4 with Gemin3 suggests that it could serve as a cofactor of this DEAD box protein. Gemin4 also interacts directly with several of the Sm core proteins. Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm. Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems. Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.

Animals↗
PubMed2000

Changes in human fasciolosis in a temperate area: about some observations over a 28-year period in central France.

A retrospective study of 616 patients affected by fasciolosis was carried out to determine the numerical fluctuations of this disease over time, the recruitment of patients, and the modes of infection in a cattle-rearing area under a temperate climate (region of Limousin, central France). The annual number of patients showed irregular fluctuations between 1955 and 1987, after which it showed subsequent decreases until 1998. Before 1980, 66.3% of the persons under study were living in villages, whereas the others inhabited larger towns. An inverse relationship was noted after 1981: 80.8% of the individuals lived in towns consisting of > 1,000 inhabitants, whereas only 19.2% resided in smaller villages. Watercress was the infection mode in 98% of persons, with infections being attributed to four watercress species before 1980 versus only two species of Nasturtium sp. after 1981. The 235 watercress beds investigated in this study were found to contain 1 or 2 Lymnaea species as follows: L. truncatula only (84% of watering places), L. glabra only (6.3%), and both species (6.3%). In the populations of L. truncatula, natural infections of snails with Fasciola hepatica were irregular and occurred up to six times over the 28-year period in the region of Limousin. According to the authors, the decrease in human cases and the changes in the recruitment of patients might be explained by the demographic movements that occurred over several decades in the region of Limousin, with the moving of younger age groups into towns.

Adolescent↗
PubMed2000

Variability of Fasciola hepatica infection in Lymnaea ovata in relation to snail population and snail age.

Bimiracidial infections of Lymnaea ovata with Fasciola hepatica were performed under laboratory conditions to determine the susceptibility of snails from six French populations to trematode infection. In five populations of L. ovata the prevalence of infection in the 1-mm groups ranged between 2.7% and 43.7% at day 35 postexposure; it decreased in the 2-mm snails and was zero in larger groups. In the snails from Thenay (periodically polluted brook) the prevalence of F. hepatica infection decreased from the 1-mm group to the 8-mm group (from 23.9% to 1.0%) and was zero in the 10-mm L. ovata. The total number of cercariae shed per snail was 18.3 in the 1-mm group, increasing to 117 in the 8-mm group. The latter findings could be interpreted as a consequence of periodic pollution in the brook of Thenay; pollution might disrupt the defense system of L. ovata and facilitate the subsequent larval development of F. hepatica.

Aging↗
PubMed2000

Prevalence of Haplometra cylindracea infection in three species of Lymnaea snails in central France.

Field investigations were performed over a 2- or 3-year period at five sites in central France to determine the prevalence of Haplometra cylindracea infection in three species of adult Lymnaea, and to compare it with that of Fasciola hepatica infection recorded in the same snails. L. glabra, L. palustris, and L. truncatula harboured Haplometra larval forms but the prevalence of this infection varied according to the site and snail species studied. The prevalences in May ranged over 0-66.9% in L. glabra, 3-7.7% in L. palustris, and 0-31.5% in L. truncatula. The mean intensity of H. cylindracea infection in May did not show any significant variation, whatever the site and species studied. The prevalence of F. hepatica infection was significantly lower in snails collected in sites known for H. cylindracea infection than in those originating from nearby meadows (0-1% instead of 1-5%). H. cylindracea could develop in some Lymnaea species and its occurrence had an impact in snails by decreasing the prevalence of F. hepatica infection.

Animals↗
PubMed2000

Prevalence of Paramphistomum daubneyi infection in cattle in central France.

Investigations at the slaughterhouse of Limoges (Central France) were performed in 1994-1996 to determine the prevalence of Paramphistomum daubneyi infection in cattle. In 1994/1995, higher prevalences of P. daubneyi were recorded in May, October, and January. In 1996, smaller variations were recorded, and prevalence in April and May was higher. The prevalence of P. daubneyi in summer was lower. Breed and age of cattle were not significantly associated to P. daubneyi infection, but females were significantly more infected than males. P daubneyi infection was related to that of Fasciola hepatica, but not to that of Dicrocoelium lanceolatum.

Abattoirs↗
PubMed2000

Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm.

We describe a novel RNA binding protein, Y14, a predominantly nuclear nucleocytoplasmic shuttling protein. Interestingly, Y14 associates preferentially with mRNAs produced by splicing but not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Y14 associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Splicing of a single intron is sufficient for Y14 association. Y14-containing nuclear complexes are different from general hnRNP complexes. They contain hnRNP proteins and several unique proteins including the mRNA export factor TAP. Thus, Y14 defines novel intermediates in the pathway of gene expression, postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic mRNPs, whose composition is established by splicing. These findings suggest that pre-mRNA splicing imprints mRNA with a unique set of proteins that persists in the cytoplasm and thereby communicates the history of the transcript.

Animals↗
PubMed2000

A field study of natural infections in three freshwater snails with Fasciola hepatica and/or Paramphistomum daubneyi in central France.

Natural infections of three freshwater snails with Fasciola hepatica and/or Paramphistomum daubneyi were studied during two periods in 1996 and 1997 (June-July and September-October) on 18 farms located in the departments of Vienne and Haute Vienne (central France), and known for low prevalences of F. hepatica infections in ruminants. A total of 1573 Lymnaea glabra and 1421 L. truncatula 6 mm high or more were collected in the meadows of 13 farms and dissected under laboratory conditions. Snails with single or concurrent infections of F. hepatica and/or

Animals↗
PubMed2000

Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein.

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by loss of FMR1 gene activity due to either lack of expression or expression of a mutant form of the protein. In mammals, FMR1 is a member of a small protein family that consists of FMR1, FXR1, and FXR2. All three members bind RNA and contain sequence motifs that are commonly found in RNA-binding proteins, including two KH domains and an RGG box. The FMR1/FXR proteins also contain a 60S ribosomal subunit interaction domain and a protein-protein interaction domain which mediates homomer and heteromer formation with each family member. Nevertheless, the specific molecular functions of FMR1/FXR proteins are unknown. Here we report the cloning and characterization of a Drosophila melanogaster homolog of the mammalian FMR1/FXR gene family. This first invertebrate homolog, termed dfmr1, has a high degree of amino acid sequence identity/similarity with the defined functional domains of the FMR1/FXR proteins. The dfmr1 product binds RNA and is similar in subcellular localization and embryonic expression pattern to the mammalian FMR1/FXR proteins. Overexpression of dfmr1 driven by the UAS-GAL4 system leads to apoptotic cell loss in all adult Drosophila tissues examined. This phenotype is dependent on the activity of the KH domains. The ability to induce a dominant phenotype by overexpressing dfmr1 opens the possibility of using genetic approaches in Drosophila to identify the pathways in which the FMR1/FXR proteins function.

Amino Acid Motifs↗
PubMed2000

The susceptibility of Lymnaea fuscus to experimental infection with Fasciola hepatica.

Three experiments on the infection of Lymnaea fuscus with Fasciola hepatica were carried out to determine if successful infections and maturation of the parasite were dependent on the size of snails at miracidial exposure. The first experiment was performed using 1-4-mm-high snails from 2 populations of L. fuscus and 1 population of Lymnaea palustris. In these snails each subjected to a single bimiracidial exposure, the prevalence of F. hepatica infection at day 35 postexposure ranged from 20.3% to 46.2% in snails measuring 1 mm in height at exposure; it was lower in the 2-mm snails and was 0 in higher size classes. The second experiment was performed by subjecting 1- and 4-mm L. fuscus to 1, 2, and 3 bimiracidial exposures. The prevalence of F. hepatica infection at day 35 postexposure was maximum in the 1-mm snails exposed once to miracidia and decreased with increasing number of exposures. The results were negative in 4-mm snails. Cercarial shedding of F. hepatica was studied in the third experiment using 1- and 2-mm L. fuscus each subjected to a single bimiracidial exposure. The total number of cercariae released from these snails was less than 50. From these results, it can be concluded that L. fuscus showed a partial resistance to F. hepatica infection due to snail age.

Animals↗
PubMed2000

Cercarial productivity of redial generations in single-miracidium infections of Lymnaea truncatula with Paramphistomum daubneyi or Fasciola hepatica.

Single-miracidium infections of Lymnaea truncatula with Paramphistomum daubneyi or with Fasciola hepatica were carried out under laboratory conditions to count free rediae, their germinal embryos, and to determine the cercarial productivity of each redial generation. In snails infected by P. daubneyi, the cercariae were produced by the first (8.7 cercariae per redia) and second (8.9 per redia) generations. At day 63 post-exposure, they corresponded, respectively, to 53.9% and 46.1% of cercariae produced by all rediae. In snails infected by F. hepatica, the majority of cercariae were produced by the R2a group (18.2 cercariae per redia) and corresponded to 66.0% of cercariae produced all rediae. The cercariae produced by the other redial groups were more limited in number: 17.5 per redia in the R1b group (28.7%) and 2.0 per redia in the R2b/R3a group (5.3%). Cercarial productivity of P. daubneyi until day 63 post-exposure was more limited in number than that of F. hepatica: a total of 145 cercariae per snail versus 427 per snail.

Animals↗
PubMed1999

Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems.

The survival of motor neurons (SMN) gene is the disease gene of spinal muscular atrophy (SMA), a common motor neuron degenerative disease. The SMN protein is part of a complex containing several proteins, of which one, SIP1 (SMN interacting protein 1), has been characterized so far. The SMN complex is found in both the cytoplasm and in the nucleus, where it is concentrated in bodies called gems. In the cytoplasm, SMN and SIP1 interact with the Sm core proteins of spliceosomal small nuclear ribonucleoproteins (snRNPs), and they play a critical role in snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing, likely by serving in the regeneration of snRNPs. Here, we report the identification of another component of the SMN complex, a novel DEAD box putative RNA helicase, named Gemin3. Gemin3 interacts directly with SMN, as well as with SmB, SmD2, and SmD3. Immunolocalization studies using mAbs to Gemin3 show that it colocalizes with SMN in gems. Gemin3 binds SMN via its unique COOH-terminal domain, and SMN mutations found in some SMA patients strongly reduce this interaction. The presence of a DEAD box motif in Gemin3 suggests that it may provide the catalytic activity that plays a critical role in the function of the SMN complex on RNPs.

Amino Acid Motifs↗
PubMed1999

Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle.

The human immunodeficiency virus type-1 Rev protein induces the nuclear export of intron-containing viral mRNAs that harbor its binding site, the Rev response element (RRE). A leucine-rich region of Rev, the activation domain, is essential for function and has been shown to be a nuclear export signal (NES). Although Rev exports viral RNAs that resemble cellular mRNAs, competition studies performed using microinjected Xenopus laevis oocytes have previously indicated that Rev utilizes a non-mRNA export pathway. Here, we show that Rev is able to induce the export of both spliceable and non-spliceable RRE-containing pre-mRNAs and that this activity is not dependent on the location of the RRE within the RNA. Importantly, even RNA molecules of different classes, such as U3 snoRNA and U6 snRNA, which are retained in the nucleus by non-pre-mRNA mechanisms, are exported to the cytoplasm in response to Rev. Consistent with the notion that Rev-mediated export of RRE-containing RNA is mechanistically distinct from the export of processed cellular mRNA, a chimeric Rev protein in which its NES is replaced by the NES of hnRNP A1 does not induce the export of a Rev-responsive mRNA. Finally, we demonstrate that Rev/RRE-activated RNA export is, like other nuclear export pathways, linked to the Ran-GTPase cycle.

Animals↗
PubMed1999

SMN mutants of spinal muscular atrophy patients are defective in binding to snRNP proteins.

Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease and the leading genetic cause of death of young children. The survival of motor neurons (SMN) gene, the SMA disease gene, is homozygously deleted or mutated in more than 98% of SMA patients. The SMN protein interacts with itself, with SMN-interacting protein 1, and with several spliceosomal small nuclear ribonucleoprotein (snRNP) Sm proteins. A complex containing SMN plays a critical role in spliceosomal snRNP assembly and in pre-mRNA splicing. SMN mutants found in SMA patients show reduced self-association and lack the capacity to regenerate the splicing machinery. Here we demonstrate that SMN mutants found in SMA patients are defective in binding to Sm proteins. Moreover, we show that SMN, but not mutants found in SMA patients, can form large oligomers and that SMN oligomerization is required for high-affinity binding to spliceosomal snRNP Sm proteins. These findings directly link the impaired interaction between SMN and Sm proteins to a defect in snRNP metabolism and to SMA.

Autoantigens↗
PubMed1999

Transportin-SR, a nuclear import receptor for SR proteins.

The SR proteins, a group of abundant arginine/serine (RS)-rich proteins, are essential pre-mRNA splicing factors that are localized in the nucleus. The RS domain of these proteins serves as a nuclear localization signal. We found that RS domain-bearing proteins do not utilize any of the known nuclear import receptors and identified a novel nuclear import receptor specific for SR proteins. The SR protein import receptor, termed transportin-SR (TRN-SR), binds specifically and directly to the RS domains of ASF/SF2 and SC35 as well as several other SR proteins. The nuclear transport regulator RanGTP abolishes this interaction. Recombinant TRN-SR mediates nuclear import of RS domain- bearing proteins in vitro. TRN-SR has amino acid sequence similarity to several members of the importin beta/transportin family. These findings strongly suggest that TRN-SR is a nuclear import receptor for the SR protein family.

Amino Acid Sequence↗
PubMed1999

Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain.

We employed a phage display system to search for proteins that interact with transportin 1 (TRN1), the import receptor for shuttling hnRNP proteins with an M9 nuclear localization sequence (NLS), and identified a short region within the N-terminus of the nucleoporin Nup153 which binds TRN1. Nup153 is located at the nucleoplasmic face of the nuclear pore complex (NPC), in the distal basket structure, and functions in mRNA export. We show that this Nup153 TRN1-interacting region is an M9 NLS. We found that both import and export receptors interact with several regions of Nup153, in a RanGTP-regulated fashion. RanGTP dissociates Nup153-import receptor complexes, but is required for Nup153-export receptor interactions. We also show that Nup153 is a RanGDP-binding protein, and that the interaction is mediated by the zinc finger region of Nup153. This represents a novel Ran-binding domain, which we term the zinc finger Ran-binding motif. We provide evidence that Nup153 shuttles between the nuclear and cytoplasmic faces of the NPC. The presence of an M9 shuttling domain in Nup153, together with its ability to move within the NPC and to interact with export receptors, suggests that this nucleoporin is a mobile component of the pore which carries export cargos towards the cytoplasm.

Amino Acid Sequence↗
PubMed1999

Molecular characterization of the hnRNP A2/B1 proteins: tissue-specific expression and novel isoforms.

hnRNP A2/B1 proteins are among the most abundant pre-mRNA-binding proteins of vertebrates and structurally similar to hnRNP A1. We have produced two specific monoclonal antibodies against A2 and B1 and studied their molecular characteristics and in vivo expression in rat tissues. Immunoprecipitation demonstrated that the hnRNP A2/B1 complexes contain many snRNP (small nuclear ribonucleoprotein) proteins, consistent with their role in pre-mRNA splicing. RNA polymerase II inhibition causes nucleocytoplasmic shuttling of A2 and B1. In most tissues, they are localized in the nucleus; however, in the squamous epithelium of the skin and esophagus A2 is also distributed in the cytoplasm. The relative amounts of A2 and B1 are not constant among different tissues. In the adrenal, only A2 is extremely abundant in the medulla but not in the cortex. In the testis the expression of A2 and B1 are observed through spermatogenesis, and different from A1 which is stringently repressed in spermatocytes. We also found and cloned a novel testis-specific isoform of A2/B1, namely hnRNP B0. The difference of expression of A2, B1, and A1 provides new information on their in vivo roles. The diversity of A/B group hnRNP proteins may have important effects on the posttranscriptional regulation of cell-specific gene expression.

Amino Acid Sequence↗