Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RRM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Norwalk virus-like food poisoning after eating oysters].

BACKGROUND: The aim of this study was to conduct a clinical-epidemiological and microbiological investigation into an outbreak of food-borne disease due to the consumption of oysters. PATIENTS AND METHODS: A historic cohort study was conducted into the consumption of 15 food items and clinical symptoms. The influence of each foodstuff was assessed by Mantel-Haenzel stratified relative risk (RRM-H) at 95% confidence intervals, and was confirmed by dose-response analysis with a chi 2 test tendency. We investigated sample stools from 5 patients and 2 food-handlers. RESULTS: The overall attack rate was 38.0% (19/50). The median period of incubation was 39.0 h (maxim 62 and minimum 3 h). The symptoms were: fever 17.6% (3/17), diarrhoea 57.9% (11/19), vomits 84.2% (16/19), nausea 89.5% (17/19) and abdominal pain 89.5% (17/19). In stratified analysis, the Mantel-Haenzel method revealed a statistically risk for oysters (RRM-H = 3.3; IC 95%: 1.1-8.7), while the RRM-H value for sea snails was not significant (RRM-H = 2.8; IC 95%: 0.9-41.1). For oyster consumption, the dose-response test was statistically significant (p = 0.005). Examination by electron microscopy revealed small round structured viruses compatible with Norwalk-like virus. The oyster contamination was reported to the public health authority. CONCLUSIONS: This research highlights the usefulness of dose-response analysis in presenting epidemiological evidence, reveals the potential role of oyster consumption in food-borne disease such us Norwalk-like virus and show the need for monitoring production centres and oyster beds in order to prevent further cases of contamination.

Adult↗
PubMed2002

Inhibition of the U1A-RNA complex by an aminoacridine derivative.

The RNA recognition motif (RRM) is one of the most common RNA binding domains. There have been few investigations of small molecule inhibitors of RRM-RNA complexes, although these inhibitors could be valuable tools for probing biological processes involving RRM-RNA complexes and would have the potential to be effective drugs. In this paper, the inhibition by small molecules of the complex formed between the N-terminal RRM of the U1A protein and stem loop 2 of U1 snRNA has been investigated. An aminoacridine derivative has been found to promote dissociation of the U1A-stem loop 2 RNA complex with an IC(50) value of 1 microM. Fluorescence experiments indicate that two aminoacridine ligands bind to each RNA target site. RNase A footprinting suggests that one binding site may be near the base pair that closes the loop and the other may be in a more flexible region of the loop. The addition of the aminoacridine derivative to stem loop 2 RNA increases the susceptibility of other portions of the loop to digestion by RNase A, which implies that binding of the ligand changes the conformation or dynamics of the stem loop target site. Either direct binding to the RNA or indirect alteration of the structure or dynamics of the loop would be likely to inhibit binding of the U1A protein to this RNA.

Aminoacridines↗
PubMed2006

Structural and functional characterization of the TgDRE multidomain protein, a DNA repair enzyme from Toxoplasma gondii.

The parasite Toxoplasma gondii expresses a 55 kDa protein or TgDRE that belongs to a novel family of proteins characterized by the presence of three domains, a human splicing factor 45-like motif (SF), a glycine-rich motif (G-patch), and a RNA recognition motif (RRM). The two latter domains are mainly known as RNA-binding domains, and their presence in TgDRE, whose partial DNA repair function was demonstrated, suggests that the protein could also be involved in the RNA metabolism. In this work, we characterized the structure and function of the different domains by using single or multidomain proteins to define their putative role. The SF45-like domain has a helical conformation and is involved in the oligomerization of the protein. The G-patch domain, mainly unstructured on its own as well as in the presence of the SF upstream and RRM downstream domains, is able to bind small RNA oligonucleotides. We also report the structure determination of the RRM domain from the NMR data. It adopts a classical betaalphabetabetaalphabeta topology consisting of a four-stranded beta sheet packed against two alpha helices but does not present the key residues for the RNA interaction. In contrast, our analysis shows that the RRM of TgDRE is not only unable to bind small RNA oligonucleotides but it also shares the protein-protein interaction characteristics with two unusual RRMs of the U2AF heterodimeric splicing factor. The presence of both RNA- and protein-binding domains seems to indicate that TgDRE could also be involved in RNA metabolism.

Amino Acid Sequence↗
PubMed2006

Separate RNA-binding surfaces on the multifunctional La protein mediate distinguishable activities in tRNA maturation.

By sequence-specific binding to 3' UUU-OH, the La protein shields precursor (pre)-RNAs from 3' end digestion and is required to protect defective pre-transfer RNAs from decay. Although La is comprised of a La motif and an RNA-recognition motif (RRM), a recent structure indicates that the RRM beta-sheet surface is not involved in UUU-OH recognition, raising questions as to its function. Progressively defective suppressor tRNAs in Schizosaccharomyces pombe reveal differential sensitivities to La and Rrp6p, a 3' exonuclease component of pre-tRNA decay. 3' end protection is compromised by mutations to the La motif but not the RRM surface. The most defective pre-tRNAs require a second activity of La, in addition to 3' protection, that requires an intact RRM surface. The two activities of La in tRNA maturation map to its two conserved RNA-binding surfaces and suggest a modular model that has implications for its other ligands.

Amino Acid Sequence↗
PubMed1997

RNA splicing specificity determined by the coordinated action of RNA recognition motifs in SR proteins.

Pre-mRNA splicing requires a large number of RNA-binding proteins that have one or more RNA-recognition motifs (RRMs). Among these is the SR protein family, whose members are essential for splicing and are able to commit pre-mRNAs to the splicing pathway with overlapping but distinct substrate specificity. Some SR proteins, such as SC35, contain an N-terminal RRM and a C-terminal arginine/serine-rich (RS) domain, whereas others, such as SF2/ASF, also contain a second, atypical RRM. Although both the RRMs and the RS domain of SR proteins are required for constitutive splicing, it is unclear which domain(s) defines their substrate specificity, and whether two RRMs in a given SR protein function independently or act coordinately. Using domain swaps between SC35 and SF2/ASF and a functional commitment assay, we demonstrate that individual domains are functional modules, RS domains are interchangeable, and substrate specificity is defined by the RRMs. The atypical RRM of SF2/ASF does not appear to function alone in splicing, but can either activate or suppress the splicing specificity of an N-terminal RRM. Therefore, multiple RRMs in SR proteins act coordinately to achieve a unique spectrum of pre-mRNA substrate specificity.

Binding Sites↗
PubMed1993

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats.

We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.

Animals↗
PubMed2001

Related eIF3 subunits TIF32 and HCR1 interact with an RNA recognition motif in PRT1 required for eIF3 integrity and ribosome binding.

eIF3 binds to 40S ribosomal subunits and stimulates recruitment of Met-tRNAiMet and mRNA to the pre-initiation complex. Saccharomyces cerevisiae contains an ortholog of human eIF3 subunit p35, HCR1, whose interactions with yeast eIF3 are not well defined. We found that HCR1 has a dual function in translation initiation: it binds to, and stabilizes, the eIF3-eIF5- eIF1-eIF2 multifactor complex and is required for the normal level of 40S ribosomes. The RNA recognition motif (RRM) of eIF3 subunit PRT1 interacted simultaneously with HCR1 and with an internal domain of eIF3 subunit TIF32 that has sequence and functional similarity to HCR1. PRT1, HCR1 and TIF32 were also functionally linked by genetic suppressor analysis. We propose that HCR1 stabilizes or modulates interaction between TIF32 and the PRT1 RRM. Removal of the PRT1 RRM resulted in dissociation of TIF32, NIP1, HCR1 and eIF5 from eIF3 in vivo, and destroyed 40S ribosome binding by the residual PRT1-TIF34-TIF35 subcomplex. Hence, the PRT1 RRM is crucial for the integrity and ribosome-binding activity of eIF3.

Alleles↗
PubMed2001

Risk-reduction mastectomy: clinical issues and research needs.

Risk-reduction mastectomy (RRM), also known as bilateral prophylactic mastectomy, is a controversial clinical option for women who are at increased risk of breast cancer. High-risk women, including women with a strong family history of breast cancer and BRCA1/2 mutation carriers, have several clinical options: risk-reduction surgery (bilateral mastectomy and bilateral oophorectomy), surveillance (mammography, clinical breast examination, and breast self-examination), and chemoprevention (tamoxifen). We review research in a number of areas central to our understanding of RRM, including recent data on 1) the effectiveness of RRM in reducing breast cancer risk, 2) the perception of RRM among women at increased risk and health-care providers, 3) the decision-making process for follow-up care of women at high risk, and 4) satisfaction and psychological status after surgery. We suggest areas of future research to better guide high-risk women and their health-care providers in the decision-making process.

Anticarcinogenic Agents↗
PubMed1993

Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors.

We present a systematic analysis of sequence motifs found in metazoan protein factors involved in constitutive pre-mRNA splicing and in alternative splicing regulation. Using profile analysis we constructed a database enriched in protein sequences containing one or more presumptive copies of the RNA-recognition motif (RRM). We provide an accurate alignment of RRMs and structure-based criteria for identifying new RRMs, including many that lack the prototype RNP-1 submotif. We present a comprehensive table of 125 sequences containing 252 RRMs, including 22 previously unreported RRMs in 17 proteins. The presence of a putative RRM in these proteins, which are implicated in a variety of cellular processes, strongly suggests that their function involves binding to RNA. Unreported homologies in the RRM-enriched database to the metazoan SR family of splicing factors are described for an Arg-rich human nuclear protein and two yeast proteins (S. pombe mei2 and S. cerevisiae Npl3). We have rigorously tested the phylogenetic relationships of a large sample of RRMs. This analysis indicates that the RRM is an ancient conserved region (ACR) that has diversified by duplication of genes and intragenic domains. Statistical analyses and classification of repeated Arg-Ser (RS) and RGG domains in various protein splicing factors are presented.

Amino Acid Sequence↗
PubMed1995

Cabeza, a Drosophila gene encoding a novel RNA binding protein, shares homology with EWS and TLS, two genes involved in human sarcoma formation.

We have previously described a partial Drosophila cDNA, clone P19, which bears homology to members of the RNA recognition motif (RRM) family of proteins [Haynes et al. (1987) Proc. Natl. Acad. Sci. USA, 84, 1819-1823]. RNA binding as well as involvement in RNA processing has been demonstrated for some RRM proteins. We report here the further characterization of P19, which we renamed cabeza (caz). caz is located on the X chromosome at position 14B. Using Northern analysis, at least four transcripts from the caz gene were observed at varying levels during development. caz mRNA and protein are enriched in the brain and central nervous system during embryogenesis. In addition, the protein is enriched in the adult head. UV crosslinking was used to demonstrate in vitro RNA binding activity for full-length recombinant caz protein and for the caz RRM domain. Sequence analysis revealed caz is related to two human genes, EWS and TLS, which are involved in chromosomal translocations. The fusion of EWS and TLS to other cellular genes results in sarcoma formation. In addition to their overall structural organization and sequence similarity, these three genes share an RRM which is divergent from typical RRMs. Therefore, it appears that these genes constitute a new sub-family of RNA binding proteins.

Amino Acid Sequence↗
PubMed1996

Two different RNA binding activities for the AU-rich element and the poly(A) sequence of the mouse neuronal protein mHuC.

HuC is one of the RNA binding proteins which are suggested to play important roles in neuronal differentiation and maintenance. We cloned and sequenced cDNAs encoding a mouse protein which is homologous to human HuC (hHuC). The longest cDNA encodes a 367 amino acid protein with three RNA recognition motifs (RRMs) and displays 96% identity to hHuC. Northern blot analysis showed that two different mRNAs, of 5.3 and 4.3 kb, for mouse HuC (mHuC) are expressed specifically in brain tissue. Comparison of cDNA sequences with the corresponding genomic sequence revealed that alternative 3' splice site selection generates two closely related mHuC isoforms. Iterative in vitro RNA selection and binding analyses showed that both HuC isoforms can bind with almost identical specificity to sequences similar to the AU-rich element (ARE), which is involved in the regulation of mRNA stability. Functional domain mapping using mHuC deletion mutants showed that the first RRM binds to ARE, that the second RRM has no RNA binding activity by itself, but facilitates ARE binding by the first RRM and that the third RRM has specific binding activity for the poly(A) sequence.

Alternative Splicing↗
PubMed2005

Tissue-dependent isoforms of mammalian Fox-1 homologs are associated with tissue-specific splicing activities.

An intronic hexanucleotide UGCAUG has been shown to play a critical role in the regulation of tissue-specific alternative splicing of pre-mRNAs in a wide range of tissues. Vertebrate Fox-1 has been shown to bind to this element, in a highly sequence-specific manner, through its RNA recognition motif (RRM). In mammals, there are at least two Fox-1-related genes, ataxin-2 binding protein 1 (A2BP1)/Fox-1 and Fxh/Rbm9, which encode an identical RRM. Here, we demonstrate that both mouse Fxh and A2BP1 transcripts undergo tissue-specific alternative splicing, generating protein isoforms specific to brain and muscle. These tissue-specific isoforms are characterized for their abilities to regulate neural cell-specific alternative splicing of a cassette exon, N30, in the non-muscle myosin heavy chain II-B pre-mRNA, previously shown to be regulated through an intronic distal downstream enhancer (IDDE). All Fxh and A2BP1 isoforms with the RRM are capable of binding to the IDDE in vitro through the UGCAUG elements. Each isoform, however, shows quantitative differences in splicing activity and nuclear distribution in transfected cells. All Fxh isoforms and a brain isoform of A2BP1 show a predominant nuclear localization. Brain isoforms of both Fxh and A2BP1 promote N30 splicing much more efficiently than do the muscle-specific isoforms. Skeletal muscles express additional isoforms that lack a part of the RRM. These isoforms are incapable of activating neural cell-specific splicing and, moreover, can inhibit UGCAUG-dependent N30 splicing. These findings suggest that tissue-specific isoforms of Fxh and A2BP1 play an important role in determining tissue specificity of UGCAUG-mediated alternative splicing.

Alternative Splicing↗
PubMed1984

Criteria for selection of decedent versus living controls in a mortality case-control study.

The mortality odds ratio computed with a decedent control series (ORD) and the mortality odds ratio obtained with a living control series (ORL) estimate the mortality rate ratio (RRM) under very different assumptions. The bias of the ORD as an estimate of RRM is a function of the mortality rates from other causes (those causes for which controls were selected) in the underlying exposed (E) and nonexposed (E) populations, while the bias of ORL as an estimate of RRM is a function of the prevalence of the study disease in the underlying E and E populations. The ORL closely estimates the RRM if the prevalence of the disease under study is small. If the study disease mortality rate is small relative to the other-causes mortality rate, the ORD closely estimates the cause-specific proportional mortality ratio.

Epidemiologic Methods↗
PubMed1988

Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present.

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.

Animals↗
PubMed2003

Investigation of the applicability of dielectric relaxation properties of amino acid solutions within the resonant recognition model.

The resonant recognition model (RRM) is a physicomathematical approach used to analyze the interactions of a protein and its target, using digital signal processing methods. The RRM is based on the finding that there is a significant correlation between the spectra of numerical presentation of protein sequences and their biological activities. Initially, the electron-ion interaction potential was used to represent each amino acid in the protein sequences. In this paper, the dielectric constant (epsilon') and dielectric loss tangent (tan delta) parameters have been determined for their possible use in the RRM. These parameters are based on the values of capacitance and conductance obtained experimentally for 20 amino acid solutions using dielectric spectroscopy for the case of the real component of dielectric permittivity; the parameter used is the dielectric increment (deltaepsilon'), the difference between dielectric constant of the amino acid solution and that of the solvent alone. The results of multiple cross-spectral analyses have shown that parameters analyzed generate in the consensus spectrum one dominant peak corresponding to the common biological activity of proteins studied, allowing the conclusion that these new parameters are suitable for use in the RRM approach.

Amino Acid Sequence↗
PubMed2000

Contribution of cytochrome P-450 omega-hydroxylase to altered arteriolar reactivity with high-salt diet and hypertension.

The present study evaluated the contribution of cytochrome P-450 omega-hydroxylase in modulating the reactivity of cremaster muscle arterioles in normotensive rats on high-salt (HS) and low-salt (LS) diet and in rats with reduced renal mass hypertension (RRM-HT). Changes in arteriolar diameter in response to ACh, sodium nitroprusside (SNP), ANG II, and elevated O(2) were measured via television microscopy under control conditions and following cytochrome P-450 omega-hydroxylase inhibition with 17-octadecynoic acid (17-ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). In normotensive rats on either LS or HS diet, resting tone was unaffected and arteriolar reactivity to ACh or SNP was minimally affected by cytochrome P-450 omega-hydroxylase inhibition. In RRM-HT rats, cytochrome P-450 omega-hydroxylase inhibition reduced resting tone and significantly enhanced arteriolar dilation to ACh and SNP. Treatment with 17-ODYA or DDMS inhibited arteriolar constriction to ANG II and O(2) in all the groups, although the degree of inhibition was greater in RRM-HT than in normotensive animals. These results suggest that metabolites of cytochrome P-450 omega-hydroxylase contribute to the altered reactivity of skeletal muscle arterioles to vasoconstrictor and vasodilator stimuli in RRM-HT.

Acetylcholine↗
PubMed1986

Prostaglandin and thromboxane formation in glomeruli from rats with reduced renal mass.

In vitro formation of prostaglandins (PG) E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 (TxB2) by glomeruli from rats with reduced renal mass (RRM) were evaluated by radioimmunoassay. Four weeks following ablation of renal mass, PGE2, PGF2 alpha, and TxB2 production by glomeruli from RRM rats was significantly greater, when compared with glomerular PG and TxB2 production of sham-operated control (C) rats. The effect of cyclooxygenase inhibition with indomethacin and the selective inhibition of thromboxane formation with UK 38485 on glomerular filtration rate (GFR) was investigated in experiments in vivo. In RRM rats indomethacin reduced GFR from 212 +/- 17 to 138 +/- 14 microliter/100 g/body weight (p less than 0.05) without effect on C rats. Thromboxane synthesis inhibition with UK 38485, however, increased GFR significantly in RRM rats (221 +/- 26 to 303 +/- 21; p less than 0.05). The data suggest that vasodilatory PGs and TxB2 modulate GFR in rats with ablation of renal mass.

Animals↗
PubMed1991

Sympathetic neural control of vascular muscle in reduced renal mass hypertension.

Vascular smooth muscle (VSM) transmembrane potentials (Em) were measured in situ in small branch arteries (150-300-microns o.d.), small branch veins (300-400-microns o.d.), arterioles (90-150-microns o.d.), and venules (80-250-microns o.d.) in the mesenteric and gracilis muscle and the arterioles and venules of cremaster muscle vascular beds in anesthetized rats with reduced renal mass hypertension (HT-RRM) and normotensive sham-operated RRM control rats. All rats were given a 4% NaCl diet for 2 weeks with water ad libitum. Relative to sham, HT-RRM mesenteric and gracilis arterial and venous vessels, but not the microvessels of the cremaster muscle bed, were less polarized during superfusion with normal physiological salt solution. Also relative to sham, hyperpolarization responses to local sympathetic neural (SNS) denervation with 6-hydroxydopamine were greater in mesenteric and gracilis small arteries, arterioles, veins, and venules but not in cremaster microvessels. The immediate (less than 5-minute) electrogenic depolarization response to local blockade of VSM Na(+)-K+ pump activity with 10(-3) M ouabain was similar between each respective HT-RRM and sham vessel pair in each vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗