Abstract:
:Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala) a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Fernández-Murray JP,Prykhozhij SV,Dufay JN,Steele SL,Gaston D,Nasrallah GK,Coombs AJ,Liwski RS,Fernandez CV,Berman JN,McMaster CRdoi
10.1371/journal.pgen.1005783subject
Has Abstractpub_date
2016-01-28 00:00:00pages
e1005783issue
1eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-02349journal_volume
12pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::The model plant species Arabidopsis thaliana is successful at colonizing land that has recently undergone human-mediated disturbance. To investigate the prehistoric spread of A. thaliana, we applied approximate Bayesian computation and explicit spatial modeling to 76 European accessions sequenced at 876 nuclear loci. ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000075
更新日期:2008-05-16 00:00:00
abstract::Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (R...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002731
更新日期:2012-06-01 00:00:00
abstract::Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improving control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008822
更新日期:2020-06-04 00:00:00
abstract::The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be perfor...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.0020188
更新日期:2006-12-29 00:00:00
abstract::Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001373
更新日期:2011-04-01 00:00:00
abstract::The catalytic subunit of yeast telomerase, Est2p, is a telomere associated throughout most of the cell cycle, while the Est1p subunit binds only in late S/G2 phase, the time of telomerase action. Est2p binding in G1/early S phase requires a specific interaction between telomerase RNA (TLC1) and Ku80p. Here, we show th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000236
更新日期:2008-10-01 00:00:00
abstract::In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004829
更新日期:2014-12-04 00:00:00
abstract::Riboviruses (RNA viruses without DNA replication intermediates) are the most abundant pathogens infecting animals and plants. Only a few riboviral infections can be controlled with antiviral drugs, mainly because of the rapid appearance of resistance mutations. Little reliable information is available concerning i) ki...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002832
更新日期:2012-01-01 00:00:00
abstract::X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., "MTMRs"). Biochemically, catalytically inacti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003583
更新日期:2013-06-01 00:00:00
abstract::HSPB7 is a member of the small heat-shock protein (HSPB) family and is expressed in the cardiomyocytes from cardiogenesis onwards. A dramatic increase in HSPB7 is detected in the heart and blood plasma immediately after myocardial infarction. Additionally, several single-nucleotide polymorphisms of HSPB7 have been ide...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006984
更新日期:2017-08-21 00:00:00
abstract::Dominant mutations in the alpha-B crystallin (CryAB) gene are responsible for a number of inherited human disorders, including cardiomyopathy, skeletal muscle myopathy, and cataracts. The cellular mechanisms of disease pathology for these disorders are not well understood. Among recent advances is that the disease sta...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003544
更新日期:2013-06-01 00:00:00
abstract::Through as yet undefined proteins and pathways, the SUMO-targeted ubiquitin ligase (STUbL) suppresses genomic instability by ubiquitinating SUMO conjugated proteins and driving their proteasomal destruction. Here, we identify a critical function for fission yeast STUbL in suppressing spontaneous and chemically induced...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001320
更新日期:2011-03-01 00:00:00
abstract::With the increasing focus of genetic association on the identification of trait-associated rare variants through sequencing, it is important to identify the most cost-effective sequencing strategies for these studies. Deep sequencing will accurately detect and genotype the most rare variants per individual, but may li...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006811
更新日期:2017-06-22 00:00:00
abstract::Reduced bacterial genomes and most genomes of cell organelles (chloroplasts and mitochondria) do not encode the full set of 32 tRNA species required to read all triplets of the genetic code according to the conventional wobble rules. Superwobbling, in which a single tRNA species that contains a uridine in the wobble p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003076
更新日期:2012-01-01 00:00:00
abstract::Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002349
更新日期:2011-11-01 00:00:00
abstract::Under nitrogen deprivation, filaments of the cyanobacterium Anabaena undergo a process of development, resulting in a one-dimensional pattern of nitrogen-fixing heterocysts separated by about ten photosynthetic vegetative cells. Many aspects of gene expression before nitrogen deprivation and during the developmental p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005031
更新日期:2015-04-01 00:00:00
abstract::Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive e...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001022
更新日期:2010-07-15 00:00:00
abstract::Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act) spliceosomes formed on site-specifically labeled pre-mRNA,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005539
更新日期:2015-09-22 00:00:00
abstract::Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tra...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006189
更新日期:2016-07-22 00:00:00
abstract::The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006414
更新日期:2016-11-07 00:00:00
abstract::Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sym...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003364
更新日期:2013-04-01 00:00:00
abstract::Zeins, the predominent storage proteins in maize endosperm, are encoded by multiple genes and gene families. However, only a few transcriptional factors for zein gene regulation have been functionally characterized. In this study, a MADS-box protein, namely ZmMADS47, was identified as an Opaque2 (O2) interacting prote...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005991
更新日期:2016-04-14 00:00:00
abstract::Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To u...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1003394
更新日期:2013-03-01 00:00:00
abstract::The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 promotes hyperadenylation by stimulating poly(A)-polymerases (PAPα/γ), but this activity has not previously been linked to the decay of endogenous transcripts. Moreover, the mechani...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005610
更新日期:2015-10-20 00:00:00
abstract::The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including Magnaporthe oryzae. A total of eight genes (MoHOX1 to MoHOX8) encoding putative homeobox transcription factors (TFs) were identified from the M. oryzae genome. Knockout mutants for each MoHOX gen...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000757
更新日期:2009-12-01 00:00:00
abstract::Exome sequencing has been widely used in detecting pathogenic nonsynonymous single nucleotide variants (SNVs) for human inherited diseases. However, traditional statistical genetics methods are ineffective in analyzing exome sequencing data, due to such facts as the large number of sequenced variants, the presence of ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004237
更新日期:2014-03-20 00:00:00
abstract::Knowledge of biological relatedness between samples is important for many genetic studies. In large-scale human genetic association studies, the estimated kinship is used to remove cryptic relatedness, control for family structure, and estimate trait heritability. However, estimation of kinship is challenging for spar...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007021
更新日期:2017-09-29 00:00:00
abstract::Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing ch...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008759
更新日期:2020-04-24 00:00:00
abstract::Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001354
更新日期:2011-03-01 00:00:00
abstract::Interpreting the impact of human genome variation on phenotype is challenging. The functional effect of protein-coding variants is often predicted using sequence conservation and population frequency data, however other factors are likely relevant. We hypothesized that variants in protein post-translational modificati...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004919
更新日期:2015-01-22 00:00:00