Abstract:
:The assimilation of nitrate, a most important soil nitrogen source, is tightly regulated in microorganisms and plants. In Aspergillus nidulans, during the transcriptional activation process of nitrate assimilatory genes, the interaction between the pathway-specific transcription factor NirA and the exportin KapK/CRM1 is disrupted, and this leads to rapid nuclear accumulation and transcriptional activity of NirA. In this work by mass spectrometry, we found that in the absence of nitrate, when NirA is inactive and predominantly cytosolic, methionine 169 in the nuclear export sequence (NES) is oxidized to methionine sulfoxide (Metox169). This oxidation depends on FmoB, a flavin-containing monooxygenase which in vitro uses methionine and cysteine, but not glutathione, as oxidation substrates. The function of FmoB cannot be replaced by alternative Fmo proteins present in A. nidulans. Exposure of A. nidulans cells to nitrate led to rapid reduction of NirA-Metox169 to Met169; this reduction being independent from thioredoxin and classical methionine sulfoxide reductases. Replacement of Met169 by isoleucine, a sterically similar but not oxidizable residue, led to partial loss of NirA activity and insensitivity to FmoB-mediated nuclear export. In contrast, replacement of Met169 by alanine transformed the protein into a permanently nuclear and active transcription factor. Co-immunoprecipitation analysis of NirA-KapK interactions and subcellular localization studies of NirA mutants lacking different parts of the protein provided evidence that Met169 oxidation leads to a change in NirA conformation. Based on these results we propose that in the presence of nitrate the activation domain is exposed, but the NES is masked by a central portion of the protein (termed nitrate responsive domain, NiRD), thus restricting active NirA molecules to the nucleus. In the absence of nitrate, Met169 in the NES is oxidized by an FmoB-dependent process leading to loss of protection by the NiRD, NES exposure, and relocation of the inactive NirA to the cytosol.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Gallmetzer A,Silvestrini L,Schinko T,Gesslbauer B,Hortschansky P,Dattenböck C,Muro-Pastor MI,Kungl A,Brakhage AA,Scazzocchio C,Strauss Jdoi
10.1371/journal.pgen.1005297subject
Has Abstractpub_date
2015-07-01 00:00:00pages
e1005297issue
7eissn
1553-7390issn
1553-7404pii
PGENETICS-D-13-02425journal_volume
11pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::The epigenetic regulation of gene expression by the covalent modification of histones is a fundamental mechanism required for the proper differentiation of germ line cells during development. Trimethylation of histone 3 lysine 9 (H3K9me3) leads to chromatin silencing and the formation of heterochromatin by recruitment...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000644
更新日期:2009-09-01 00:00:00
abstract::Alternative splicing generates protein diversity and allows for post-transcriptional gene regulation. Estimates suggest that 10% of the genes in Caenorhabditis elegans undergo alternative splicing. We constructed a splicing-sensitive microarray to detect alternative splicing for 352 cassette exons and tested for chang...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000001
更新日期:2008-02-29 00:00:00
abstract::Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coord...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002822
更新日期:2012-01-01 00:00:00
abstract::In many cases protein assemblies are stabilized by covalent bonds, one example of which is the formation of intra- or intermolecular ε-(γ-glutamyl)lysil cross-links catalyzed by transglutaminases (TGases). Because of the potential for unwanted cross-linking reactions, the activities of many TGases have been shown to b...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007912
更新日期:2019-04-08 00:00:00
abstract::Ribosome assembly cofactors are widely conserved across all domains of life. One such group, the ribosome-associated GTPases (RA-GTPase), act as molecular switches to coordinate ribosome assembly. We previously identified the Staphylococcus aureus RA-GTPase Era as a target for the stringent response alarmone (p)ppGpp,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008346
更新日期:2019-08-29 00:00:00
abstract::Studies in model organisms suggest that epistasis may play an important role in the etiology of complex diseases and traits in humans. With the era of large-scale genome-wide association studies fast approaching, it is important to quantify whether it will be possible to detect interacting loci using realistic sample ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020157
更新日期:2006-09-22 00:00:00
abstract::An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene-envi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002482
更新日期:2012-01-01 00:00:00
abstract::Somatic mutations in the nuclear genome are required for tumor formation, but the functional consequences of somatic mitochondrial DNA (mtDNA) mutations are less understood. Here we identify somatic mtDNA mutations across 527 tumors and 14 cancer types, using an approach that takes advantage of evidence from both geno...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005333
更新日期:2015-06-30 00:00:00
abstract::Mp is an irradiation-induced mouse mutation associated with microphthalmia, micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1(Mp)) mRNA has a frameshi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003998
更新日期:2013-01-01 00:00:00
abstract::Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resu...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1005568
更新日期:2015-11-05 00:00:00
abstract::Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m(5)C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004110
更新日期:2014-02-06 00:00:00
abstract::Unlike mammals and birds, teleost fish undergo external embryogenesis, and therefore their embryos are constantly challenged by stresses from their living environment. These stresses, when becoming too harsh, will cause arrest of cell proliferation, abnormal cell death or senescence. Such organisms have to evolve a so...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005881
更新日期:2016-02-22 00:00:00
abstract::Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp produ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008941
更新日期:2020-08-06 00:00:00
abstract::Human chromosome 15q25 is involved in several disease-associated structural rearrangements, including microdeletions and chromosomal markers with inverted duplications. Using comparative fluorescence in situ hybridization, strand-sequencing, single-molecule, real-time sequencing and Bionano optical mapping analyses, w...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008075
更新日期:2019-03-27 00:00:00
abstract::The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arise...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006835
更新日期:2017-06-12 00:00:00
abstract::Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous muta...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002114
更新日期:2011-07-01 00:00:00
abstract::Phenotypes extracted from Electronic Health Records (EHRs) are increasingly prevalent in genetic studies. EHRs contain hundreds of distinct clinical laboratory test results, providing a trove of health data beyond diagnoses. Such lab data is complex and lacks a ubiquitous coding scheme, making it more challenging than...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1009077
更新日期:2020-11-11 00:00:00
abstract::A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call n...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003605
更新日期:2013-01-01 00:00:00
abstract::The rate of germline mutation varies widely between species but little is known about the extent of variation in the germline mutation rate between individuals of the same species. Here we demonstrate that an allele that increases the rate of germline mutation can result in a distinctive signature in the genomic regio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006549
更新日期:2017-01-17 00:00:00
abstract::Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effect...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002294
更新日期:2011-09-01 00:00:00
abstract::Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and ver...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005402
更新日期:2015-09-03 00:00:00
abstract::The cerebellum is a pivotal centre for the integration and processing of motor and sensory information. Its extended development into the postnatal period makes this structure vulnerable to a variety of pathologies, including neoplasia. These properties have prompted intensive investigations that reveal not only devel...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1008630
更新日期:2020-04-16 00:00:00
abstract::Ocular coloboma results from abnormal embryonic development and is often associated with additional ocular and systemic features. Coloboma is a highly heterogeneous disorder with many cases remaining unexplained. Whole exome sequencing from two cousins affected with dominant coloboma with microcornea, cataracts, and s...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005002
更新日期:2015-02-26 00:00:00
abstract::Many microbes exhibit quorum sensing (QS) to cooperate, share and perform a social task in unison. Recent studies have shown the emergence of reversible phenotypic heterogeneity in the QS-responding pathogenic microbial population under laboratory conditions as a possible bet-hedging survival strategy. However, very l...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008395
更新日期:2019-09-17 00:00:00
abstract::Down syndrome (DS), commonly caused by an extra copy of chromosome 21 (chr21), occurs in approximately one out of 700 live births. Precisely how an extra chr21 causes over 80 clinically defined phenotypes is not yet clear. Reduced representation bisulfite sequencing (RRBS) analysis at single base resolution revealed D...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003515
更新日期:2013-06-01 00:00:00
abstract::Increases in fruit weight of cultivated vegetables and fruits accompanied the domestication of these crops. Here we report on the positional cloning of a quantitative trait locus (QTL) controlling fruit weight in tomato. The derived allele of Cell Size Regulator (CSR-D) increases fruit weight predominantly through enl...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006930
更新日期:2017-08-17 00:00:00
abstract::Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000095
更新日期:2008-06-13 00:00:00
abstract::Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driv...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000849
更新日期:2010-02-19 00:00:00
abstract::Genomic regions that are unusually divergent between closely related species or racial groups can be particularly informative about the process of speciation or the operation of natural selection. The two sequenced genomes of cultivated Asian rice, Oryza sativa, reveal that at least 6% of the genomes are unusually div...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020199
更新日期:2006-11-17 00:00:00
abstract::North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by ...
journal_title:PLoS genetics
pub_type: 历史文章,杂志文章
doi:10.1371/journal.pgen.1002397
更新日期:2012-01-01 00:00:00