Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The iron regulatory protein (IRP) is a cytoplasmic RNA-binding protein that regulates cellular iron metabolism at the posttranscriptional level. IRP is an unusual bifunctional molecule: in iron-replete cells it predominantly exists as a 4Fe-4S protein and exhibits aconitase enzymatic activity, whereas apo-IRP prevails in iron-starved cells and binds to iron-responsive elements (IREs), structural motifs within the untranslated regions of mRNAs involved in iron metabolism. A related protein with iron-regulated IRE-binding activity, IRPB, was previously identified in rodent cells. IRE-binding by IRP and IRPB is induced by iron deprivation and nitric oxide (NO). Controversial hypotheses have proposed that the induction of IRE-binding activity by iron results either from de novo synthesis of the apo-protein or from a posttranslational conversion of the Fe-S to the apo-protein form. This prompted a detailed analysis of how iron and NO regulate the RNA-binding activities of IRP and IRPB. We demonstrate that IRP is a relatively stable protein (half-life > 12 h). The induction of IRE-binding does not require de novo protein synthesis but results from conversion of Fe-S IRP to apo-IRP. In contrast, IRPB appears less stable in nonstarved cells (half-life approximately 4-6 h) and must be synthesized de novo following iron starvation. Our results furthermore reveal that two RNA-binding proteins with close structural and functional similarities that respond to the same cellular signals are regulated by predominantly different mechanisms.
 ...
PMID:Differential regulation of two related RNA-binding proteins, iron regulatory protein (IRP) and IRPB. 758 45

The hfq-encoded RNA-binding protein HF-I has long been known as a host factor for phage Qbeta RNA replication and has recently been shown to be essential for translation of rpoS, which encodes the sigmaS subunit of RNA polymerase. Here we demonstrate that an hfq null mutant does not synthesize glycogen, is starvation and multiple stress sensitive, and exhibits strongly reduced expression of representative sigmaS-regulated genes. These phenotypes are consistent with strongly reduced sigmaS levels in the hfq mutant. However, the analysis of global protein synthesis patterns on two-dimensional O'Farrell gels indicates that approximately 40% of the more than 30 proteins whose syntheses are altered in the hfq null mutant are not affected by an rpoS mutation. We conclude that HF-I is a global regulator involved in the regulation of expression of sigmaS and sigmaS-independent genes.
 ...
PMID:The RNA-binding protein HF-I plays a global regulatory role which is largely, but not exclusively, due to its role in expression of the sigmaS subunit of RNA polymerase in Escherichia coli. 898 15

The fission yeast Schizosaccharomyces pombe initiates sexual development under starved conditions. Nutritional starvation decreases the level of intracellular cAMP. This decrease induces expression of the ste11 gene, which encodes a key transcription factor for genes required for mating and meiosis. Mutational analyses of S. pombe genes encoding components of the cAMP cascade have shown that S. pombe cells stay in the mitotic cell cycle as long as the level of cAMP-dependent protein kinase activity is high, but are committed to mating and meiosis if this activity is lowered. To initiate meiosis in S. pombe, a protein kinase encoded by pat1 (also called ran1) should be inactivated. This inactivation results from deprivation of nutrients via a cascade of expression of genes including ste11. The mei2 gene encodes a factor indispensable for the initiation of meiosis, and its expression is regulated directly by Ste11. If Pat1 kinase is intact, it blocks Mei2 function. Mei2 is required at two distinct stages of meiosis, once prior to premeiotic DNA synthesis and then prior to the first meiotic division (meiosis I). Mei2 is an RNA-binding protein, and forms a complex with a specific RNA species to promote meiosis I. This RNA species, named meiRNA, is polyadenylated but is unlikely to encode a protein product. It is essential for meiosis I, but not for either cell growth or premeiotic DNA synthesis. These observations unequivocally demonstrate that RNA plays a critical role in the control of meiosis.
 ...
PMID:Regulation of meiosis in fission yeast. 911 52

The fragile X syndrome results from a transcriptional silencing of the FMR1 gene and the absence of its encoded protein. FMRP is a cytoplasmic RNA-binding protein, whose specific cellular function is still unknown. We present evidence that virtually all detectable cytoplasmic FMRP in mouse NIH 3T3 and human HeLa cells is found strictly in association with mRNA in actively translating polyribosomes. Furthermore, FMRP released from polyribosomes is associated with ribonucleoprotein complexes with sedimentation coefficients of 60-70S and selection on oligo(dT)-cellulose reveals that this association is specific to poly(A)-containing mRNPs. This association with actively translating polyribosomes is not affected by alteration of translational processes induced by serum stimulation and starvation in NIH 3T3 cells, suggesting that FMR1 expression is not cell cycle regulated and that FMRP might have a house-keeping function. FXR2 protein, which is closely related to FMRP, is also detected associated with mRNPs in translating polyribosomes. The results strongly suggest that FMRP might be a mRNA chaperone interacting with mRNP complexes.
 ...
PMID:The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes. 928 83

The OxyS regulatory RNA integrates the adaptive response to hydrogen peroxide with other cellular stress responses and protects against DNA damage. Among the OxyS targets is the rpoS-encoded sigma(s) subunit of RNA polymerase. Sigma(s) is a central regulator of genes induced by osmotic stress, starvation and entry into stationary phase. We examined the mechanism whereby OxyS represses rpoS expression and found that the OxyS RNA inhibits translation of the rpoS message. This repression is dependent on the hfq-encoded RNA-binding protein (also denoted host factor I, HF-I). Co-immunoprecipitation and gel mobility shift experiments revealed that the OxyS RNA binds Hfq, suggesting that OxyS represses rpoS translation by altering Hfq activity.
 ...
PMID:The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein. 977 49

Brucella abortus is a facultative intracellular pathogen that causes abortion and infertility in domestic animals and a severe debilitating febrile illness in humans. The mechanisms that this highly successful intracellular pathogen uses to adapt to, and survive within, the harsh intracellular environment of the host macrophage are presently unknown. Maintenance of the stationary phase growth state has been proposed to be critical for the virulence of several mammalian pathogens, but analysis of this relationship for the brucellae has not been undertaken. In order to evaluate this relationship, we examined the in vitro and in vivo characteristics of an isogenic hfq mutant constructed from virulent Brucella abortus 2308. In Escherichia coli, the hfq gene product is an RNA-binding protein that participates in the regulation of stationary phase stress resistance, at least partly by enhancing translation of the stationary phase-specific sigma factor RpoS. As expected, the Brucella abortus hfq mutant, designated Hfq3, showed increased sensitivity to H2O2, and decreased survival under acidic conditions (pH 4.0), during stationary phase growth compared with 2308. Hfq3 was also less able to withstand prolonged starvation than 2308. The Brucella abortus hfq mutant, unlike its parental strain 2308, fails to replicate in cultured murine macrophages, and is rapidly cleared from the spleens and livers of experimentally infected BALB/c mice. These findings suggest that the Brucella abortus hfq gene product makes an essential contribution to pathogenesis in mice, probably by allowing the brucellae to adapt appropriately to the harsh environmental conditions encountered within the host macrophage.
 ...
PMID:The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice. 1056 9

Sexual differentiation in the fission yeast Schizosaccharomyces pombe is triggered by nutrient starvation or by the presence of mating pheromones. We identified a novel gene, msa1, which encodes a 533-aa putative RNA-binding protein that inhibits sexual differentiation. Disruption of the msa1 gene caused cells to hypersporulate. Intracellular levels of msa1 RNA and Msa1 protein diminished after several hours of nitrogen starvation. Genetic analysis suggested that the function of msa1 is independent of the cAMP pathway and stress-responsive pathway. Deletion of the ras1 gene in diploid cells inhibited sporulation and in haploid cells decreased expression of mating-pheromone-induced genes such as mei2, mam2, ste11, and rep1; simultaneous deletion of msa1 reversed both phenotypes. Overexpression of msa1 decreased activated Ras1(Val17)-induced expression of mam2. Phenotypic hypersporulation was similar between cells with deletion of only rad24 and both msa1 and rad24, but simultaneous deletion of msa1 and msa2/nrd1 additively increased hypersporulation. Therefore, we suggest that the primary function of Msa1 is to negatively regulate sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway.
 ...
PMID:A novel gene, msa1, inhibits sexual differentiation in Schizosaccharomyces pombe. 1516 38

Recent studies have uncovered dozens of regulatory small RNAs in bacteria. A large number of these small RNAs act by pairing to their target mRNAs. The outcome of pairing can be either stimulation or inhibition of translation. Pairing in vivo frequently depends on the RNA-binding protein Hfq. Synthesis of these small RNAs is tightly regulated at the level of transcription; many of the well-studied stress response regulons have now been found to include a regulatory RNA. Expression of the small RNA can help the cell cope with environmental stress by redirecting cellular metabolism, exemplified by RyhB, a small RNA expressed upon iron starvation. Although small RNAs found in Escherichia coli can usually be identified by sequence comparison to closely related enterobacteria, other approaches are necessary to find the equivalent RNAs in other bacterial species. Nonetheless, it is becoming increasingly clear that many if not all bacteria encode significant numbers of these important regulators. Tracing their evolution through bacterial genomes remains a challenge.
 ...
PMID:Small RNA regulators and the bacterial response to stress. 1738 Dec 74

Hypoxia and other adverse conditions are commonly encountered by rapidly growing cells. The RNA-binding protein RBM3 (RNA-binding motif protein 3), which is transcriptionally induced by low temperature and hypoxia, has recently been implicated in survival of colon cancer cells by mechanisms involving cyclooxygenase-2 (COX-2) signaling. Immunohistochemically, we found strong RBM3 expression in a variety of malignant and proliferating tissues but low expression in resting and terminally differentiated cells. RBM3 expression in fibroblasts and human embryonal kidney (HEK293) cells subjected to serum deprivation or contact inhibition closely paralleled proliferation rates, assessed by real-time RT-PCR and immunoblotting. siRNA-mediated RBM3 knockdown reduced cell viability and finally led to cell death, which did not involve caspase-3-mediated apoptosis, cell cycle arrest, or COX-2 regulation. In contrast, RBM3 over-expression rescued cells from death under serum starvation. This was associated with increased translation rates, as measured by C serine and H phenylalanine incorporation. Together, RBM3 is a critical factor providing cellular survival advantages in an adverse microenvironment presumably by restoring translation efficacy.
 ...
PMID:The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. 1977 Jun 90

Cellular adaptations to stress often involve changes in RNA metabolism. One RNA-binding protein that has been implicated in RNA handling during environmental stress in both animal cells and prokaryotes is the Ro autoantigen. However, the function of Ro in stress conditions has been unknown. We report that a Ro protein in the radiation-resistant eubacterium Deinococcus radiodurans participates in ribosomal RNA (rRNA) degradation during growth in stationary phase, a form of starvation. Levels of the Ro ortholog Rsr increase dramatically during growth in stationary phase and the presence of Rsr confers a growth advantage. Examination of rRNA profiles reveals that Rsr, the 3' to 5' exoribonuclease polynucleotide phosphorylase (PNP) and additional nucleases are all involved in the extensive rRNA decay that occurs during starvation of this bacterium. We show that Rsr, PNP, and an Rsr-PNP complex exhibit increased sedimentation with ribosomal subunits during stationary phase. As the fractionation of PNP with ribosomal subunits is strongly enhanced in the presence of Rsr, we propose that Ro proteins function as cofactors to increase the association of exonucleases with certain substrates during stress.
 ...
PMID:A role for a bacterial ortholog of the Ro autoantigen in starvation-induced rRNA degradation. 2016 Jan 19


1 2 3 4 Next >>