Faculty Opinions recommendation of Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline.

2018 ◽  
Author(s):  
Peter Boag
Keyword(s):  
Binding Sites ◽  
C Elegans ◽  
Regulatory Landscape

scholarly journals Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline

Cell ◽  
2018 ◽  
Vol 172 (5) ◽  
pp. 937-951.e18 ◽  
Author(s):  
En-Zhi Shen ◽  
Hao Chen ◽  
Ahmet R. Ozturk ◽  
Shikui Tu ◽  
Masaki Shirayama ◽  
...  
Keyword(s):  
Binding Sites ◽  
C Elegans ◽  
Regulatory Landscape

scholarly journals Identification of piRNA binding sites reveals the Argonaute regulatory landscape of the C. elegans germline

2018 ◽  
Author(s):  
En-Zhi Shen ◽  
Hao Chen ◽  
Ahmet R. Ozturk ◽  
Shikui Tu ◽  
Masaki Shirayama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Small Rnas ◽  
Cross Linking ◽  
Computational Studies ◽  
Germline Gene ◽  
C Elegans ◽  
Transcriptional Regulatory ◽  
Regulatory Landscape

SUMMARYpiRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post transcriptional regulatory step in germline gene expression.

lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1373-1383 ◽  
Author(s):  
S. Christensen ◽  
V. Kodoyianni ◽  
M. Bosenberg ◽  
L. Friedman ◽  
J. Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Binding Sites ◽  
Feedback Loop ◽  
Target Genes ◽  
Sequence Similarity ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Downstream Target ◽  
Binding Factor ◽  
Flanking Regions

The homologous receptors LIN-12 and GLP-1 mediate diverse cell-signaling events during development of the nematode Caenorhabditis elegans. These two receptors appear to be functionally interchangeable and have sequence similarity to Drosophila Notch. Here we focus on a molecular analysis of the lag-1 gene (lin-12 -and glp-1), which plays a central role in LIN-12 and GLP-1-mediated signal transduction. We find that the predicted LAG-1 protein is homologous to two DNA-binding proteins: human C Promoter Binding Factor (CBF1) and Drosophila Suppressor of Hairless (Su(H)). Furthermore, we show that LAG-1 binds specifically to the DNA sequence RTGGGAA, previously identified as a CBF-1/Su(H)-binding site. Finally, we report that the 5′ flanking regions and first introns of the lin-12, glp-1 and lag-1 genes are enriched for potential LAG-1-binding sites. We propose that LAG-1 is a transcriptional regulator that serves as a primary link between the LIN-12 and GLP-1 receptors and downstream target genes in C. elegans. In addition, we propose that LAG-1 may be a key component of a positive feedback loop that amplifies activity of the LIN-12/GLP-1 pathway.

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

scholarly journals A transcription factor collective defines the HSN serotonergic neuron regulatory landscape

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Carla Lloret-Fernández ◽  
Miren Maicas ◽  
Carlos Mora-Martínez ◽  
Alejandro Artacho ◽  
Ángela Jimeno-Martín ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Specific Cell ◽  
Serotonergic Neuron ◽  
C Elegans ◽  
Mouse Orthologs ◽  
Deep Homology ◽  
Regulatory Landscape ◽  
Neuronal Type ◽  
Selection Of

Cell differentiation is controlled by individual transcription factors (TFs) that together activate a selection of enhancers in specific cell types. How these combinations of TFs identify and activate their target sequences remains poorly understood. Here, we identify the cis-regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in Caenorhabditis elegans. Activation of the HSN transcriptome is directly orchestrated by a collective of six TFs. Binding site clusters for this TF collective form a regulatory signature that is sufficient for de novo identification of HSN neuron functional enhancers. Among C. elegans neurons, the HSN transcriptome most closely resembles that of mouse serotonergic neurons. Mouse orthologs of the HSN TF collective also regulate serotonergic differentiation and can functionally substitute for their worm counterparts which suggests deep homology. Our results identify rules governing the regulatory landscape of a critically important neuronal type in two species separated by over 700 million years.

scholarly journals MK-801 is a potent nematocidal agent. Characterization of MK-801 binding sites in Caenorhabditis elegans

1989 ◽  
Vol 260 (3) ◽  
pp. 923-926 ◽  
Author(s):  
J M Schaeffer ◽  
A R Bergstrom ◽  
M J Turner
Keyword(s):  
Caenorhabditis Elegans ◽  
Binding Site ◽  
Binding Sites ◽  
Mammalian Brain ◽  
Apparent Dissociation Constant ◽  
Mk 801 ◽  
C Elegans ◽  
Mammalian Tissues ◽  
Free Living Nematode

MK-801, an N-methyl-D-aspartate antagonist in mammalian brain tissue, is a potent nematocidal agent. Specific MK-801 binding sites have been identified and characterized in a membrane fraction prepared from the free-living nematode Caenorhabditis elegans. The high-affinity MK-801 binding site has an apparent dissociation constant, Kd, of 225 nM. Unlike the MK-801 binding site in mammalian tissues, the C. elegans binding site is not effected by glutamate or glycine, and polyamines are potent inhibitors of specific MK-801 binding.

unc-53 controls longitudinal migration in C. elegans

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3367-3379 ◽  
Author(s):  
Eve Stringham ◽  
Nathalie Pujol ◽  
Joel Vandekerckhove ◽  
Thierry Bogaert
Keyword(s):  
Binding Sites ◽  
Adaptor Protein ◽  
Direct Interaction ◽  
Actin Binding ◽  
C Elegans ◽  
Guidance Cues ◽  
Preferred Direction ◽  
Excretory Canals ◽  
Novel Protein

Cell migration and outgrowth are thought to be based on analogous mechanisms that require repeated cycles of process extension, reading and integration of multiple directional signals, followed by stabilisation in a preferred direction, and renewed extension. We have characterised a C. elegans gene, unc-53, that appears to act cell autonomously in the migration and outgrowth of muscles, axons and excretory canals. Abrogation of unc-53 function disrupts anteroposterior outgrowth in those cells that normally express the gene. Conversely, overexpression of unc-53 in bodywall muscles leads to exaggerated outgrowth. UNC-53 is a novel protein conserved in vertebrates that contains putative SH3- and actin-binding sites. unc-53 interacts genetically with sem-5 and we demonstrated a direct interaction in vitro between UNC-53 and the SH2-SH3 adaptor protein SEM-5/GRB2. Thus, unc-53 is involved in longitudinal navigation and might act by linking extracellular guidance cues to the intracellular cytoskeleton.

scholarly journals SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Wenke Wang ◽  
Amaresh Chaturbedi ◽  
Minghui Wang ◽  
Serim An ◽  
Satheeja Santhi Velayudhan ◽  
...  
Keyword(s):  
Heat Stress ◽  
Stress Response ◽  
Binding Sites ◽  
Target Genes ◽  
Germline Development ◽  
Heat Stress Response ◽  
C Elegans ◽  
Redundant Functions

C. elegans SET-9 and SET-26 are highly homologous paralogs that share redundant functions in germline development, but SET-26 alone plays a key role in longevity and heat stress response. Whereas SET-26 is broadly expressed, SET-9 is only detectable in the germline, which likely accounts for their different biological roles. SET-9 and SET-26 bind to H3K4me3 with adjacent acetylation marks in vitro and in vivo. In the soma, SET-26 acts through DAF-16 to modulate longevity. In the germline, SET-9 and SET-26 restrict H3K4me3 domains around SET-9 and SET-26 binding sites, and regulate the expression of specific target genes, with critical consequence on germline development. SET-9 and SET-26 are highly conserved and our findings provide new insights into the functions of these H3K4me3 readers in germline development and longevity.

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