Abstract:
:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the imprinted gene UBE3A. Individuals with AS suffer from intellectual disability, speech impairment, and motor dysfunction. Currently there is no cure for the disease. Here, we evaluated the phenotypic effect of activating the silenced paternal allele of Ube3a by depleting its antisense RNA Ube3a-ATS in mice. Premature termination of Ube3a-ATS by poly(A) cassette insertion activates expression of Ube3a from the paternal chromosome, and ameliorates many disease-related symptoms in the AS mouse model, including motor coordination defects, cognitive deficit, and impaired long-term potentiation. Studies on the imprinting mechanism of Ube3a revealed a pattern of biallelic transcription initiation with suppressed elongation of paternal Ube3a, implicating transcriptional collision between sense and antisense polymerases. These studies demonstrate the feasibility and utility of unsilencing the paternal copy of Ube3a via targeting Ube3a-ATS as a treatment for Angelman syndrome.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Meng L,Person RE,Huang W,Zhu PJ,Costa-Mattioli M,Beaudet ALdoi
10.1371/journal.pgen.1004039subject
Has Abstractpub_date
2013-01-01 00:00:00pages
e1004039issue
12eissn
1553-7390issn
1553-7404pii
PGENETICS-D-13-01872journal_volume
9pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Intraflagellar transport (IFT) particles or trains are composed of IFT-A and IFT-B complexes. To assess the working mechanism of the IFT-A complex in IFT and ciliogenesis, we have analyzed ift43 mutants of Chlamydomnonas in conjunction with mutants of the other IFT-A subunits. An ift43 null mutant or a mutant with a p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006627
更新日期:2017-02-16 00:00:00
abstract::In oocytes, where centrosomes are absent, the chromosomes direct the assembly of a bipolar spindle. Interactions between chromosomes and microtubules are essential for both spindle formation and chromosome segregation, but the nature and function of these interactions is not clear. We have examined oocytes lacking two...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005605
更新日期:2015-10-16 00:00:00
abstract::Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In co...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002130
更新日期:2011-06-01 00:00:00
abstract::Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton moti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004800
更新日期:2014-11-13 00:00:00
abstract::Seam cells in Caenorhabditis elegans provide a paradigm for the stem cell mode of division, with the ability to both self-renew and produce daughters that differentiate. The transcription factor RNT-1 and its DNA binding partner BRO-1 (homologues of the mammalian cancer-associated stem cell regulators RUNX and CBFβ, r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002200
更新日期:2011-08-01 00:00:00
abstract::The unfolded protein response (UPR) is an adaptive signaling pathway utilized to sense and alleviate the stress of protein folding in the endoplasmic reticulum (ER). In mammals, the UPR is mediated through three proximal sensors PERK/PEK, IRE1, and ATF6. PERK/PEK is a protein kinase that phosphorylates the alpha subun...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0010037
更新日期:2005-09-01 00:00:00
abstract::Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive o...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004393
更新日期:2014-06-12 00:00:00
abstract::The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003261
更新日期:2013-01-01 00:00:00
abstract::One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryoni...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000912
更新日期:2010-04-15 00:00:00
abstract::The ribonuclease III enzyme Drosha has a central role in the biogenesis of microRNA (miRNA) by binding and cleaving hairpin structures in primary RNA transcripts into precursor miRNAs (pre-miRNAs). Many miRNA genes are located within protein-coding host genes and cleaved by Drosha in a manner that is coincident with s...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004312
更新日期:2014-05-01 00:00:00
abstract::Teleost fishes, thanks to their rapid evolution of sex determination mechanisms, provide remarkable opportunities to study the formation of sex chromosomes and the mechanisms driving the birth of new master sex determining (MSD) genes. However, the evolutionary interplay between the sex chromosomes and the MSD genes t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008013
更新日期:2019-08-22 00:00:00
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::The coordination of growth with nutritional status is essential for proper development and physiology. Nutritional information is mostly perceived by peripheral organs before being relayed to the brain, which modulates physiological responses. Hormonal signaling ensures this organ-to-organ communication, and the failu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005209
更新日期:2015-05-28 00:00:00
abstract::Fpr1 (FK506-sensitive proline rotamase 1), a protein of the FKBP12 (FK506-binding protein 12 kDa) family in Saccharomyces cerevisiae, is a primary target for the immunosuppressive agents FK506 and rapamycin. Fpr1 inhibits calcineurin and TORC1 (target of rapamycin complex 1) when bound to FK506 and rapamycin, respecti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008865
更新日期:2020-06-30 00:00:00
abstract::Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecL(L) . Ou...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003809
更新日期:2013-01-01 00:00:00
abstract::Light is one of the most important environmental cues regulating multiple aspects of plant growth and development, and abscisic acid (ABA) is a plant hormone that plays important roles during many phases of the plant life cycle and in plants' responses to various environmental stresses. How plants integrate the extern...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004197
更新日期:2014-02-27 00:00:00
abstract::XRN2 is a conserved 5'→3' exoribonuclease that complexes with proteins that contain XRN2-binding domains (XTBDs). In Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes XRN2 to retain its activity. XRN2 activity is also promoted by 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1) through hydrolysis of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006313
更新日期:2016-09-15 00:00:00
abstract::Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella spec...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007389
更新日期:2018-05-14 00:00:00
abstract::Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in D...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004756
更新日期:2014-11-13 00:00:00
abstract::Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002968
更新日期:2012-01-01 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::The lipopolysaccharide O-antigen structure expressed by the European Helicobacter pylori model strain G27 encompasses a trisaccharide, an intervening glucan-heptan and distal Lewis antigens that promote immune escape. However, several gaps still remain in the corresponding biosynthetic pathway. Here, systematic mutage...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008497
更新日期:2019-11-20 00:00:00
abstract::Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central n...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000511
更新日期:2009-06-01 00:00:00
abstract::Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0010048
更新日期:2005-10-01 00:00:00
abstract::In response to stress and injury a coordinated activation of conserved signalling modules, such as JNK and JAK/STAT, is critical to trigger regenerative tissue restoration. While these pathways rebuild homeostasis and promote faithful organ recovery, it is intriguing that they also become activated in various tumour c...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007187
更新日期:2018-01-22 00:00:00
abstract::Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-trans...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002062
更新日期:2011-05-01 00:00:00
abstract::Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002136
更新日期:2011-06-01 00:00:00
abstract::Filamentous fungi produce diverse secondary metabolites (SMs) essential to their ecology and adaptation. Although each SM is typically produced by only a handful of species, global SM production is governed by widely conserved transcriptional regulators in conjunction with other cellular processes, such as development...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005096
更新日期:2015-03-18 00:00:00
abstract::We recently showed that cassette integration and deletion in integron platforms were occurring through unconventional site-specific recombination reactions involving only the bottom strand of attC sites. The lack of sequence conservation among attC sites led us to hypothesize that sequence-independent structural recog...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000632
更新日期:2009-09-01 00:00:00
abstract::The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present in each species' native ecological niche. In a new environment, however, the same bacteria may grow poorly due to regulatory constraints or biochemical deficiencies. Adaptation to ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003617
更新日期:2013-01-01 00:00:00