Abstract:
:One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the awarding of the Nobel Prize in Physiology or Medicine to Capecchi, Evans, and Smithies for their pioneering work in targeted recombination mutagenesis in mammals. Another noteworthy discovery made nearly a decade ago was the identification of a novel class of non-coding genes called microRNAs. MicroRNAs are among the largest known classes of regulatory elements with more than 1000 predicted to exist in the mouse genome. Over 50% of known microRNAs are located within introns of coding genes. Given that currently about half of the genes in mouse have been knocked out, we investigated the possibility that intronic microRNAs may have been coincidentally deleted or disrupted in some of these mouse models. We searched published murine knockout studies and gene trap embryonic stem cell line databases for cases where a microRNA was located within or near the manipulated genomic loci, finding almost 200 cases where microRNA expression may have been disrupted along with another gene. Our results draw attention to the need for careful planning in future knockout studies to minimize the unintentional disruption of microRNAs. These data also raise the possibility that many knockout studies may need to be reexamined to determine if loss of a microRNA contributes to the phenotypic consequences attributed to loss of a protein-encoding gene.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Osokine I,Hsu R,Loeb GB,McManus MTdoi
10.1371/journal.pgen.0040034subject
Has Abstractpub_date
2008-02-01 00:00:00pages
e34issue
2eissn
1553-7390issn
1553-7404pii
07-PLGE-RA-0544journal_volume
4pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3' untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression var...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005987
更新日期:2016-04-27 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::The kinetochore is the central molecular machine that drives chromosome segregation in all eukaryotes. Genetic studies have suggested that protein sumoylation plays a role in regulating the inner kinetochore; however, the mechanism remains elusive. Here, we show that Saccharomyces cerevisiae Ulp2, an evolutionarily co...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008477
更新日期:2019-11-20 00:00:00
abstract::Pre-mRNAs are often processed in complex patterns in tissue-specific manners to produce a variety of protein isoforms from single genes. However, mechanisms orchestrating the processing of the entire transcript are not well understood. Muscle-specific alternative pre-mRNA processing of the unc-60 gene in Caenorhabditi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002991
更新日期:2012-01-01 00:00:00
abstract::Intercellular communication mediated by gap junction (GJ) proteins is indispensable during embryogenesis, tissue regeneration and wound healing. Here we report functional analysis of a gap junction protein, Innexin 2 (Inx2), in cell type specification during Drosophila oogenesis. Our data reveal a novel involvement of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006542
更新日期:2017-01-23 00:00:00
abstract::Resequencing is an emerging tool for identification of rare disease-associated mutations. Rare mutations are difficult to tag with SNP genotyping, as genotyping studies are designed to detect common variants. However, studies have shown that genetic heterogeneity is a probable scenario for common diseases, in which mu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000384
更新日期:2009-02-01 00:00:00
abstract::The Unfolded Protein Response (UPR) maintains homeostasis in the endoplasmic reticulum (ER) and defends against ER stress, an underlying factor in various human diseases. During the UPR, numerous genes are activated that sustain and protect the ER. These responses are known to involve the canonical UPR transcription f...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003701
更新日期:2013-01-01 00:00:00
abstract::Gene expression can be highly heterogeneous in isogenic cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessar...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005047
更新日期:2015-06-25 00:00:00
abstract::There is growing evidence that gene expression profiling of peripheral blood cells is a valuable tool for assessing gene signatures related to exposure, drug-response, or disease. However, the true promise of this approach can not be estimated until the scientific community has robust baseline data describing variatio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000873
更新日期:2010-03-12 00:00:00
abstract::Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the domin...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002412
更新日期:2011-12-01 00:00:00
abstract::Arsenic is a well-established human carcinogen of poorly understood mechanism of genotoxicity. It is generally accepted that arsenic acts indirectly by generating oxidative DNA damage that can be converted to replication-dependent DNA double-strand breaks (DSBs), as well as by interfering with DNA repair pathways and ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003640
更新日期:2013-01-01 00:00:00
abstract::We have developed a powerful experimental framework that combines competitive selection and microarray-based genetic footprinting to comprehensively reveal the genetic basis of bacterial behaviors. Application of this method to Escherichia coli motility identifies 95% of the known flagellar and chemotaxis genes, and r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030154
更新日期:2007-09-01 00:00:00
abstract::During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regul...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003278
更新日期:2013-01-01 00:00:00
abstract::The presence of 5-methylcytidine (m(5)C) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage of low-throughput methods. To obtain a high resolution, systematic, and ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003602
更新日期:2013-06-01 00:00:00
abstract::Because cohesion prevents sister-chromatid separation and spindle elongation, cohesion dissolution may trigger these two events simultaneously. However, the relatively normal spindle elongation kinetics in yeast cohesin mutants indicates an additional mechanism for the temporal control of spindle elongation. Here we s...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003319
更新日期:2013-01-01 00:00:00
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 ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005297
更新日期:2015-07-01 00:00:00
abstract::At the molecular level, the evolution of new traits can be broadly divided between changes in gene expression and changes in protein-coding sequence. For proteins, the evolution of novel functions is generally thought to proceed through sequential point mutations or recombination of whole functional units. In Saccharo...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007786
更新日期:2019-04-04 00:00:00
abstract::Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008923
更新日期:2020-07-31 00:00:00
abstract::Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000099
更新日期:2008-06-20 00:00:00
abstract::The genetics of domestication has been extensively studied ever since the rediscovery of Mendel's law of inheritance and much has been learned about the genetic control of trait differences between crops and their ancestors. Here, we ask how domestication has altered genetic architecture by comparing the genetic archi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008791
更新日期:2020-05-14 00:00:00
abstract::Meiotic cytokinesis influences the fertility and ploidy of gametes. However, limited information is available on the genetic control of meiotic cytokinesis in plants. Here, we identified a rice mutant with low male fertility, defective callose in meiosis 1 (dcm1). The pollen grains of dcm1 are proved to be defective i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007769
更新日期:2018-11-12 00:00:00
abstract::Endoreplication is a cell cycle variant that entails cell growth and periodic genome duplication without cell division, and results in large, polyploid cells. Cells switch from mitotic cycles to endoreplication cycles during development, and also in response to conditional stimuli during wound healing, regeneration, a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008253
更新日期:2019-07-10 00:00:00
abstract::Starvation of cells for the DNA building block dTTP is strikingly lethal (thymineless death, TLD), and this effect is observed in all organisms. The phenomenon, discovered some 60 years ago, is widely used to kill cells in anticancer therapies, but many questions regarding the precise underlying mechanisms have remain...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004310
更新日期:2014-05-08 00:00:00
abstract::Proteins associated with familial neurodegenerative disease often aggregate in patients' neurons. Several such proteins, e.g. TDP-43, aggregate and are toxic when expressed in yeast. Deletion of the ATXN2 ortholog, PBP1, reduces yeast TDP-43 toxicity, which led to identification of ATXN2 as an amyotrophic lateral scle...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008308
更新日期:2019-08-07 00:00:00
abstract::Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism. The activity of Akt must be carefully balanced, as increased Akt signaling is frequently associated with cancer and as insufficient Akt signaling is...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000990
更新日期:2010-06-17 00:00:00
abstract::Neuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans α-tubulin gene mec-12 that trigger...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004715
更新日期:2014-11-13 00:00:00
abstract::The lineage factor Foxp3 is essential for the development and maintenance of regulatory T cells, but little is known about the mechanisms involved. Here, we demonstrate that an N-terminal proline-rich interaction region is crucial for Foxp3's function. Subdomains within this key region link Foxp3 to several independen...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005251
更新日期:2015-06-24 00:00:00
abstract::The differentiation of cells into distinct cell types, each of which is heritable for many generations, underlies many biological phenomena. White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types, each thought to be adapted to unique niches within their human host. To systemat...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001070
更新日期:2010-08-19 00:00:00
abstract::Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the sp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002262
更新日期:2011-09-01 00:00:00
abstract::Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005907
更新日期:2016-03-15 00:00:00