scholarly journals Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype

2011 ◽  
Vol 194 (5) ◽  
pp. 789-805 ◽  
Author(s):  
Jennifer L. Rohn ◽  
David Sims ◽  
Tao Liu ◽  
Marina Fedorova ◽  
Frieder Schöck ◽  
...  
Keyword(s):  
Rna Interference ◽  
Rna Splicing ◽  
Actin Binding ◽  
Nuclear Actin ◽  
Systematic Method ◽  
The Core ◽  
Binding Domains ◽  
Genome Wide ◽  
Number Of Genes ◽  
Conserved Core

Although a large number of actin-binding proteins and their regulators have been identified through classical approaches, gaps in our knowledge remain. Here, we used genome-wide RNA interference as a systematic method to define metazoan actin regulators based on visual phenotype. Using comparative screens in cultured Drosophila and human cells, we generated phenotypic profiles for annotated actin regulators together with proteins bearing predicted actin-binding domains. These phenotypic clusters for the known metazoan “actinome” were used to identify putative new core actin regulators, together with a number of genes with conserved but poorly studied roles in the regulation of the actin cytoskeleton, several of which we studied in detail. This work suggests that although our search for new components of the core actin machinery is nearing saturation, regulation at the level of nuclear actin export, RNA splicing, ubiquitination, and other upstream processes remains an important but unexplored frontier of actin biology.

scholarly journals Isolation and properties of two actin-binding domains in gelsolin.

1985 ◽  
Vol 260 (28) ◽  
pp. 15232-15238 ◽  
Author(s):  
D J Kwiatkowski ◽  
P A Janmey ◽  
J E Mole ◽  
H L Yin
Keyword(s):  
Actin Binding ◽  
Binding Domains

Genome-Wide RNA Interference: Functional Genomics in the Postgenomics Era

2017 ◽  
Vol 2017 (9) ◽  
pp. pdb.top097550 ◽  
Author(s):  
Katerina Politi ◽  
Narendra Wajapeyee
Keyword(s):  
Rna Interference ◽  
Functional Genomics ◽  
Genome Wide

Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes

2017 ◽  
Vol 128 ◽  
pp. 39-46 ◽  
Author(s):  
Lizhe Zhu ◽  
Hanlun Jiang ◽  
Fu Kit Sheong ◽  
Xuefeng Cui ◽  
Yanli Wang ◽  
...  
Keyword(s):  
Rna Interference ◽  
The Core

scholarly journals A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets

2013 ◽  
Vol 20 (5) ◽  
pp. 1135-1145 ◽  
Author(s):  
Sophia Adamia ◽  
Benjamin Haibe-Kains ◽  
Patrick M. Pilarski ◽  
Michal Bar-Natan ◽  
Samuel Pevzner ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Rna Splicing ◽  
Myeloid Leukemia ◽  
Therapeutic Targets ◽  
Disease Markers ◽  
Genome Wide ◽  
A Genome ◽  
Aberrant Rna ◽  
Acute Myeloid

scholarly journals GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background

2020 ◽  
Author(s):  
Nasa Sinnott-Armstrong ◽  
Sahin Naqvi ◽  
Manuel Rivas ◽  
Jonathan K Pritchard
Keyword(s):  
Complex Traits ◽  
Genetic Basis ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Biological Processes ◽  
Uk Biobank ◽  
The Core ◽  
Genome Wide ◽  
Core Genes

SummaryGenome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. However, for most traits it remains difficult to interpret what genes and biological processes are impacted by the top hits. Here, as a contrast, we describe UK Biobank GWAS results for three molecular traits—urate, IGF-1, and testosterone—that are biologically simpler than most diseases, and for which we know a great deal in advance about the core genes and pathways. Unlike most GWAS of complex traits, for all three traits we find that most top hits are readily interpretable. We observe huge enrichment of significant signals near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of variation in each trait, including insights into differences in testosterone regulation between females and males. Meanwhile, in other respects the results are reminiscent of GWAS for more-complex traits. In particular, even these molecular traits are highly polygenic, with most of the variance coming not from core genes, but from thousands to tens of thousands of variants spread across most of the genome. Given that diseases are often impacted by many distinct biological processes, including these three, our results help to illustrate why so many variants can affect risk for any given disease.

scholarly journals FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression

2021 ◽  
Author(s):  
Ricardo N Ramirez ◽  
Kaitavjeet Chowdhary ◽  
Juliette Leon ◽  
Diane Mathis ◽  
Christophe Benoist
Keyword(s):  
Gene Expression ◽  
Chromatin Immunoprecipitation ◽  
T Regulatory Cells ◽  
Gene Clusters ◽  
Specific Gene ◽  
Regulatory Cells ◽  
Proximity Ligation ◽  
The Core ◽  
Transcriptional Cofactors ◽  
Number Of Genes

Gene expression programs are specified by higher-order chromatin structure and enhancer-promoter loops (EPL). T regulatory cells (Treg) identity is dominantly specified by the transcription factor FoxP3, whose mechanism of action is unclear. We applied proximity-ligation with chromatin immunoprecipitation (HiChIP) in Treg and closely related conventional CD4+ T cells (Tconv). EPL identified by H3K27Ac HiChIP showed a range of connection intensity, with some super-connected genes. TF-specific HiChIP showed that FoxP3 interacts with EPLs at a large number of genes, including some not differentially expressed in Treg vs Tconv, but enriched at the core Treg signature loci that it upregulates. FoxP3 association correlates with heightened H3H27Ac looping, as ascertained by analysis of FoxP3-deficient Treg-like cells. There was marked asymmetry in the loci where FoxP3 associated at the enhancer- or the promoter-side of EPLs, with enrichment for different transcriptional cofactors. FoxP3 EPL intensity distinguished gene clusters identified by single-cell ATAC-seq as co-varying between individual Tregs, supporting a direct transactivation model for FoxP3 in determining Treg identity.

scholarly journals Reciprocal action of Casein Kinase Iε on core planar polarity proteins regulates clustering and asymmetric localisation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Helen Strutt ◽  
Jessica Gamage ◽  
David Strutt
Keyword(s):  
Core Protein ◽  
Intercellular Junctions ◽  
Casein Kinase ◽  
Planar Polarity ◽  
The Core ◽  
Pupal Wing ◽  
Polarity Proteins ◽  
Conserved Core

The conserved core planar polarity pathway is essential for coordinating polarised cell behaviours and the formation of polarised structures such as cilia and hairs. Core planar polarity proteins localise asymmetrically to opposite cell ends and form intercellular complexes that link the polarity of neighbouring cells. This asymmetric segregation is regulated by phosphorylation through poorly understood mechanisms. We show that loss of phosphorylation of the core protein Strabismus in the Drosophila pupal wing increases its stability and promotes its clustering at intercellular junctions, and that Prickle negatively regulates Strabismus phosphorylation. Additionally, loss of phosphorylation of Dishevelled – which normally localises to opposite cell edges to Strabismus – reduces its stability at junctions. Moreover, both phosphorylation events are independently mediated by Casein Kinase Iε. We conclude that Casein Kinase Iε phosphorylation acts as a switch, promoting Strabismus mobility and Dishevelled immobility, thus enhancing sorting of these proteins to opposite cell edges.

scholarly journals DoChaP: The Domain Change Presenter

2020 ◽  
Author(s):  
Shani T. Gal-Oz ◽  
Nimrod Haiat ◽  
Dana Eliyahu ◽  
Guy Shani ◽  
Tal Shay
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Protein Domains ◽  
Visual Presentation ◽  
Structural Effect ◽  
Protein Isoforms ◽  
Multiple Transcripts ◽  
Genome Wide ◽  
Health And Disease ◽  
Specific Alternative

AbstractAlternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

scholarly journals Functional Comparison of the Tup11 and Tup12 Transcriptional Corepressors in Fission Yeast

2005 ◽  
Vol 25 (2) ◽  
pp. 716-727 ◽  
Author(s):  
Fredrik Fagerström-Billai ◽  
Anthony P. H. Wright
Keyword(s):  
Gene Expression ◽  
Gene Duplication ◽  
Fission Yeast ◽  
Budding Yeast ◽  
Functional Difference ◽  
Evolutionary Mechanism ◽  
Genome Wide ◽  
Number Of Genes ◽  
Transcriptional Corepressors ◽  
Genome Wide Gene Expression

ABSTRACT Gene duplication is considered an important evolutionary mechanism. Unlike many characterized species, the fission yeast Schizosaccharomyces pombe contains two paralogous genes, tup11 + and tup12 + , that encode transcriptional corepressors similar to the well-characterized budding yeast Tup1 protein. Previous reports have suggested that Tup11 and Tup12 proteins play redundant roles. Consistently, we show that the two Tup proteins can interact together when expressed at normal levels and that each can independently interact with the Ssn6 protein, as seen for Tup1 in budding yeast. However, tup11 − and tup12 − mutants have different phenotypes on media containing KCl and CaCl2. Consistent with the functional difference between tup11 − and tup12 − mutants, we identified a number of genes in genome-wide gene expression experiments that are differentially affected by mutations in the tup11 + and tup12 + genes. Many of these genes are differentially derepressed in tup11 − mutants and are over-represented in genes that have previously been shown to respond to a range of different stress conditions. Genes specifically derepressed in tup12 − mutants require the Ssn6 protein for their repression. As for Tup12, Ssn6 is also required for efficient adaptation to KCl- and CaCl2-mediated stress. We conclude that Tup11 and Tup12 are at least partly functionally diverged and suggest that the Tup12 and Ssn6 proteins have adopted a specific role in regulation of the stress response.

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