Abstract:
:Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Jang AR,Moravcevic K,Saez L,Young MW,Sehgal Adoi
10.1371/journal.pgen.1004974subject
Has Abstractpub_date
2015-02-12 00:00:00pages
e1004974issue
2eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-01876journal_volume
11pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Almost 60 years ago, Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase (PNPase). Although this discovery provided an important tool for deciphering the genetic code, subsequent work revealed that the predominant functi...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1007654
更新日期:2018-10-11 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::House dust mites are common pests with an unusual evolutionary history, being descendants of a parasitic ancestor. Transition to parasitism is frequently accompanied by genome rearrangements, possibly to accommodate the genetic change needed to access new ecology. Transposable element (TE) activity is a source of geno...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007183
更新日期:2018-01-29 00:00:00
abstract::While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002003
更新日期:2011-02-03 00:00:00
abstract::In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007560
更新日期:2018-08-13 00:00:00
abstract::The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infecti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004056
更新日期:2014-01-01 00:00:00
abstract::Enterobacter sp. 638 is an endophytic plant growth promoting gamma-proteobacterium that was isolated from the stem of poplar (Populus trichocarpaxdeltoides cv. H11-11), a potentially important biofuel feed stock plant. The Enterobacter sp. 638 genome sequence reveals the presence of a 4,518,712 bp chromosome and a 157...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000943
更新日期:2010-05-13 00:00:00
abstract::In non-motile fungi, sexual reproduction relies on strong morphogenetic changes in response to pheromone signaling. We report here on a systematic screen for morphological abnormalities of the mating process in fission yeast Schizosaccharomyces pombe. We derived a homothallic (self-fertile) collection of viable deleti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006721
更新日期:2017-04-14 00:00:00
abstract::DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukary...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003920
更新日期:2013-10-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005131.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1006300
更新日期:2016-08-31 00:00:00
abstract::Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutation...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006470
更新日期:2017-01-12 00:00:00
abstract::Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of "modular...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0010034
更新日期:2005-09-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1008320.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1008556
更新日期:2019-12-19 00:00:00
abstract::Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 23...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1002432
更新日期:2012-01-01 00:00:00
abstract::The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003586
更新日期:2013-01-01 00:00:00
abstract::Protein homeostasis is critical for cell survival and functions during stress and is regulated at both RNA and protein levels. However, how the cell integrates RNA-processing programs with post-translational protein quality control systems is unknown. Transactive response DNA-binding protein (TARDBP/TDP-43) is an RNA-...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004693
更新日期:2014-10-16 00:00:00
abstract::DNA interstrand crosslinks (ICLs) are among the most toxic types of damage to a cell. For this reason, many ICL-inducing agents are effective therapeutic agents. For example, cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA (PUVA) is useful for treating psoriasis. However, repair mech...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000189
更新日期:2008-09-12 00:00:00
abstract::The vast majority of meiotic recombination events (crossovers (COs) and non-crossovers (NCOs)) cluster in narrow hotspots surrounded by large regions devoid of recombinational activity. Here, using a new molecular approach in plants, called "pollen-typing", we detected and characterized hundreds of CO and NCO molecule...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003922
更新日期:2013-11-01 00:00:00
abstract::Steroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the evolutionarily cons...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003085
更新日期:2012-01-01 00:00:00
abstract::Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in ext...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001007
更新日期:2010-07-08 00:00:00
abstract::High glucose diets are unhealthy, although the mechanisms by which elevated glucose is harmful to whole animal physiology are not well understood. In Caenorhabditis elegans, high glucose shortens lifespan, while chemically inflicted glucose restriction promotes longevity. We investigated the impact of glucose metaboli...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008982
更新日期:2020-08-25 00:00:00
abstract::Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels ar...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003475
更新日期:2013-05-01 00:00:00
abstract::Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identifi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020047
更新日期:2006-04-01 00:00:00
abstract::Differences in transcriptional regulatory networks underlie much of the phenotypic variation observed across organisms. Changes to cis-regulatory elements are widely believed to be the predominant means by which regulatory networks evolve, yet examples of regulatory network divergence due to transcription factor (TF) ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005011
更新日期:2015-03-06 00:00:00
abstract::The use of autozygosity as a mapping tool in the search for autosomal recessive disease genes is well established. We hypothesized that autozygosity not only unmasks the recessiveness of disease causing variants, but can also reveal natural knockouts of genes with less obvious phenotypic consequences. To test this hyp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004030
更新日期:2013-01-01 00:00:00
abstract::The genome of the fission yeast Schizosaccharomyces pombe encodes 17 kinases that are essential for cell growth. These include the cell-cycle regulator Cdc2, as well as several kinases that coordinate cell growth, polarity, and morphogenesis during the cell cycle. In this study, we further characterized another of the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005768
更新日期:2016-01-05 00:00:00
abstract::A universal Tree of Life (TOL) has long been a goal of molecular phylogeneticists, but reticulation at the level of genes and possibly at the levels of cells and species renders any simple interpretation of such a TOL, especially as applied to prokaryotes, problematic. ...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1005912
更新日期:2016-04-14 00:00:00
abstract::The rate at which genomes adapt to environmental changes and the prevalence of adaptive processes in molecular evolution are two controversial issues in current evolutionary genetics. Previous attempts to quantify the genome-wide rate of adaptation through amino-acid substitution have revealed a surprising diversity o...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005774
更新日期:2016-01-11 00:00:00
abstract::To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 w...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1002718
更新日期:2012-07-01 00:00:00
abstract::Despite the well-documented role of remote enhancers in controlling developmental gene expression, the mechanisms that allocate enhancers to genes are poorly characterized. Here, we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered chrom...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004897
更新日期:2015-01-08 00:00:00