scholarly journals Olfactory receptor–dependent receptor repression in Drosophila

2021 ◽  
Vol 7 (32) ◽  
pp. eabe3745
Author(s):  
Kaan Mika ◽  
Steeve Cruchet ◽  
Phing Chian Chai ◽  
Lucia L. Prieto-Godino ◽  
Thomas O. Auer ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Regulatory Networks ◽  
Receptor Gene ◽  
Gene Array ◽  
Receptor Expression ◽  
Specific Gene ◽  
Coding Region ◽  
Ionotropic Receptor ◽  
Olfactory Systems ◽  
In Cis

In olfactory systems across phyla, most sensory neurons express a single olfactory receptor gene selected from a large genomic repertoire. We describe previously unknown receptor gene–dependent mechanisms that ensure singular expression of receptors encoded by a tandem gene array [Ionotropic receptor 75c (Ir75c), Ir75b, and Ir75a, organized 5′ to 3′] in Drosophila melanogaster. Transcription from upstream genes in the cluster runs through the coding region of downstream loci and inhibits their expression in cis, most likely via transcriptional interference. Moreover, Ir75c blocks accumulation of other receptor proteins in trans through a protein-dependent, posttranscriptional mechanism. These repression mechanisms operate in endogenous neurons, in conjunction with cell type–specific gene regulatory networks, to ensure unique receptor expression. Our data provide evidence for inter-olfactory receptor regulation in invertebrates and highlight unprecedented, but potentially widespread, mechanisms for ensuring exclusive expression of chemosensory receptors, and other protein families, encoded by tandemly arranged genes.

scholarly journals Olfactory receptor-dependent receptor repression in Drosophila

2021 ◽  
Author(s):  
Kaan Mika ◽  
Steeve Cruchet ◽  
Phing Chian Chai ◽  
Lucia L. Prieto-Godino ◽  
Thomas O. Auer ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Receptor ◽  
Receptor Gene ◽  
Gene Array ◽  
Receptor Regulation ◽  
Olfactory Receptor Gene ◽  
Transcriptional Interference ◽  
Coding Region ◽  
Receptor Proteins ◽  
Olfactory Systems

AbstractIn olfactory systems across phyla, most sensory neurons transcribe a single olfactory receptor gene selected from a large genomic repertoire. We describe novel receptor gene-dependent mechanisms that ensure singular expression of receptors encoded by a tandem gene array in Drosophila. Transcription from upstream genes in the cluster runs through the coding region of downstream loci to inhibit their expression in cis, via transcriptional interference. Moreover, one receptor blocks expression of other receptor proteins in trans through a post-transcriptional mechanism. These repression mechanisms operate in endogenous neurons to ensure their unique expression. Our data provide evidence for inter-olfactory receptor regulation in invertebrates, and highlight unprecedented, but potentially widespread, mechanisms for ensuring exclusive expression of chemosensory receptors, and other protein families, encoded by tandemly-arranged genes.

Spatially Organized Response Zones in Rat Olfactory Epithelium

1997 ◽  
Vol 77 (4) ◽  
pp. 1950-1962 ◽  
Author(s):  
John W. Scott ◽  
Donna E. Shannon ◽  
Jeff Charpentier ◽  
Lisa M. Davis ◽  
Craig Kaplan
Keyword(s):  
Gene Expression ◽  
Functional Groups ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Receptor Gene ◽  
Chemical Properties ◽  
Receptor Expression ◽  
Response Distribution ◽  
Chemical Structures ◽  
Four Electrodes

Scott, John W., Donna E. Shannon, Jeff Charpentier, Lisa M. Davis, and Craig Kaplan. Spatially organized response zones in rat olfactory epithelium. J. Neurophysiol. 77: 1950–1962, 1997. Electroolfactogram recordings were made with a four-electrode assembly from the olfactory epithelium overlying the endoturbinate bones facing the nasal septum. In this study we tested whether odors of different chemical structures produce maximal responses along longitudinally oriented regions following the olfactory receptor gene expression zones described in the literature. The distribution of responses along the dorsal-to-ventral direction of this epithelium (i.e., across the expression zones) was tested in two types of experiments. In one, four electrodes were fixed along the dorsal-to-ventral axis of one turbinate bone. In the other, four electrodes were placed in corresponding positions on four turbinate bones and moved together up toward the top of the bone. These experiments compared the odorants limonene and α-terpinene, which are simple hydrocarbons, with carvone and menthone, which differ from the hydrocarbons by the presence of ketone groups. All responses were standardized to an amyl acetate or ethyl butyrate standard. The responses to limonene and α-terpinene were often larger for the ventral electrodes. The responses to carvone and menthone were largest for the dorsal electrodes. Intermediate electrodes gave responses that were intermediate in amplitude for these odors. The possibility that direction of air flow caused the observed response distributions was directly tested in experiments with odor nozzles placed in two positions. The relatively larger dorsal responses to carvone and relatively larger ventral responses to limonene were present despite odor nozzle position. We conclude that the responses to this set of odors vary systematically in a fashion parallel to the four gene expression zones. The odorant property that governs this response distribution may be related to the presence of oxygen-containing functional groups. Certain odors evoked larger responses at the intermediate electrode sites than at other sites. Cineole was the best example of this effect. This observation shows that not all oxygen-containing functional groups produce the same effect. Although we cannot exclude other possible mechanisms, these three response gradients may be produced by the four receptor expression zones described for many of the putative olfactory receptor genes. Therefore many of the receptors in each zone may share common properties. It remains to be determined whether this zonal input is significant in central odor processing. However, the correlation of odor chemical properties with the structure of receptor molecules in each zone may provide significant leads to structure-function relationships in vertebrate olfaction.

scholarly journals Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons.

2019 ◽  
Author(s):  
If Barnes ◽  
Ximena Ibarra-Soria ◽  
Stephen Fitzgerald ◽  
Jose Gonzalez ◽  
Claire Davidson ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Receptor Gene ◽  
Gene Repertoire ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Sequences ◽  
Coding Regions ◽  
Or Gene ◽  
Or Genes ◽  
Human And Mouse

Abstract Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

scholarly journals Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons

2019 ◽  
Author(s):  
If H. A. Barnes ◽  
Ximena Ibarra-Soria ◽  
Stephen Fitzgerald ◽  
Jose M. Gonzalez ◽  
Claire Davidson ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Receptor Gene ◽  
Gene Repertoire ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Sequences ◽  
Coding Regions ◽  
Or Gene ◽  
Or Genes ◽  
Human And Mouse

ABSTRACTOlfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

scholarly journals Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics

2019 ◽  
Vol 45 (4) ◽  
pp. 656-665 ◽  
Author(s):  
Stephen K. Amoah ◽  
Brian A. Rodriguez ◽  
Constantine N. Logothetis ◽  
Praveen Chander ◽  
Carl M. Sellgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glutamate Receptor ◽  
Receptor Gene ◽  
Cell Communication ◽  
Receptor Expression ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Ionotropic Receptor ◽  
History Of ◽  
A Cell

AbstractThe ability of small secretory microvesicles known as exosomes to influence neuronal and glial function via their microRNA (miRNA) cargo has positioned them as a novel and effective method of cell-to-cell communication. However, little is known about the role of exosome-secreted miRNAs in the regulation of glutamate receptor gene expression and their relevance for schizophrenia (SCZ) and bipolar disorder (BD). Using mature miRNA profiling and quantitative real-time PCR (qRT-PCR) in the orbitofrontal cortex (OFC) of SCZ (N = 29; 20 male and 9 female), BD (N = 26; 12 male and 14 female), and unaffected control (N = 25; 21 male and 4 female) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors, was increased at the mature miRNA level in the OFC of SCZ and BD patients with positive history of psychosis at the time of death and was inversely associated with deficits in the expression of its targets glutamate ionotropic receptor NMDA-type subunit 2B (GRIN2B) and glutamate ionotropic receptor AMPA-type subunit 2 (GRIA2). Furthermore, changes in miR-223 levels in the OFC were positively and negatively correlated with inflammatory and GABAergic gene expression, respectively. Moreover, miR-223 was found to be enriched in astrocytes and secreted via exosomes, and antipsychotics were shown to control its cellular and exosomal localization in a cell-specific manner. Furthermore, addition of astrocytic exosomes in neuronal cultures resulted in a significant increase in miR-223 expression and a notable reduction in Grin2b and Gria2 mRNA levels, which was strongly inversely associated with miR-223 expression. Lastly, inhibition of astrocytic miR-223 abrogated the exosomal-mediated reduction in neuronal Grin2b expression. Taken together, our results demonstrate that the exosomal secretion of a psychosis-altered and glial-enriched miRNA that controls neuronal gene expression is regulated by antipsychotics.

Primary structure of rat HGF receptor and induced expression in glomerular mesangial cells

1996 ◽  
Vol 271 (3) ◽  
pp. F679-F688 ◽  
Author(s):  
Y. Liu ◽  
E. M. Tolbert ◽  
A. M. Sun ◽  
L. D. Dworkin
Keyword(s):  
Mesangial Cells ◽  
Rat Kidney ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Tyrosine Kinase Receptor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Coding Region ◽  
Simultaneous Induction

The c-met protooncogene encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF). It has been widely suggested that HGF and its receptor constitute a paracrine signaling system, in which mesenchymally derived cells produce ligand that binds to the receptor predominantly expressed on cells of epithelial origin. In this study, we have isolated and completely sequenced the entire coding region of c-met cDNA from the rat kidney. The nucleotide sequence of the rat c-met cDNA revealed that the HGF receptor is encoded within single open-reading frame as 190 kDa of a transmembrane glycoprotein consisting of 1,382 amino acids. Determination of c-met mRNA levels in various tissues revealed a widespread expression of c-met with the highest levels in kidney, lung, and liver. We found simultaneous induction of both HGF and its receptor gene expression by interleukin-6 (IL-6) in primary cultured rat glomerular mesangial cells. The expression of HGF and c-met was remarkably stimulated following incubation of rat mesangial cells with IL-6, in a time- and dose-dependent manner Our data suggest that autocrine action of HGF may be achieved in vivo through simultaneous induction of both HGF and its receptor expression in renal mesenchymal cells.

scholarly journals Isolation and characterization of the human interleukin-9 receptor gene

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3199-3205 ◽  
Author(s):  
MS Chang ◽  
G Engel ◽  
C Benedict ◽  
R Basu ◽  
J McNinch
Keyword(s):  
Cell Line ◽  
Fusion Gene ◽  
Genomic Structure ◽  
Receptor Gene ◽  
Mouse Fibroblast ◽  
Noncoding Region ◽  
Receptor Expression ◽  
Coding Region ◽  
Isolation And Characterization ◽  
Interleukin 9

Abstract To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5′ noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5′ noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells.

scholarly journals Decoding the olfactory map: targeted transcriptomics link olfactory receptors to glomeruli

2021 ◽  
Author(s):  
Kevin Zhu ◽  
Shawn Burton ◽  
Maira Nagai ◽  
Justin Silverman ◽  
Claire De March ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
High Throughput ◽  
Olfactory Receptor ◽  
Specific Activity ◽  
Olfactory Receptors ◽  
Receptor Expression ◽  
Central Neurons ◽  
Target Capture ◽  
Olfactory Systems ◽  
Peripheral Sensory

Abstract Sensory processing in olfactory systems is organized across olfactory bulb glomeruli, wherein axons of peripheral sensory neurons expressing the same olfactory receptor co-terminate to transmit receptor-specific activity to central neurons. Understanding how receptors map to glomeruli is therefore critical to understanding olfaction. High-throughput spatial transcriptomics is a rapidly advancing field, but low-abundance olfactory receptor expression within glomeruli has previously precluded high-throughput mapping of receptors to glomeruli. Here we combined sequential sectioning along the anteroposterior, dorsoventral, and mediolateral axes with target capture enrichment sequencing to overcome low-abundance target expression. This strategy allowed us to spatially map 86% of olfactory receptors across the olfactory bulb and uncover a relationship between OR sequence and glomerular position.

scholarly journals Minireview: Developmental Regulation of Thyrotropin Receptor Gene Expression in the Fetal and Newborn Thyroid

Endocrinology ◽  
2004 ◽  
Vol 145 (9) ◽  
pp. 4058-4061 ◽  
Author(s):  
Rosalind S. Brown
Keyword(s):  
Gene Expression ◽  
Developmental Regulation ◽  
High Titer ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Tsh Receptor ◽  
Specific Gene ◽  
Loss Of Function ◽  
Fetal Thyroid ◽  
Receptor Gene Expression

Abstract The TSH receptor plays a pivotal role in thyroid gland growth, function, and differentiation in the mature animal, but only recently has its role in the fetus and neonate been examined. Observational studies comparing the developmental regulation of TSH receptor gene expression, with thyroid morphology, and thyroid-specific gene expression in the rodent model, are reviewed in the context of older literature. Together, these data strongly suggest that the TSH receptor is essential for terminal thyroid maturation and growth but is not involved in early thyroid organogenesis or migration. Consistent with the aforementioned studies in rodents, babies with a loss of function mutation of the TSH receptor as well as babies born to mothers with potent TSH receptor-blocking antibodies have hypothyroidism and hypoplastic, but normally located, thyroid glands. Because the TSH receptor is probably not expressed in human fetuses before 10–12 wk gestation when thyroid organogenesis and migration are complete, these data provide strong evidence that human chorionic gonadotropin, which peaks in the first trimester of human pregnancy, could not play a role in fetal thyroid development. Similarly, these data imply strongly that maternal TSH receptor antibodies, when present in high titer, are of major importance in influencing fetal thyroid function only after mid-pregnancy when, by analogy with rodents, increased TSH receptor expression is likely to occur.

scholarly journals Isolation and characterization of the human interleukin-9 receptor gene

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3199-3205
Author(s):  
MS Chang ◽  
G Engel ◽  
C Benedict ◽  
R Basu ◽  
J McNinch
Keyword(s):  
Cell Line ◽  
Fusion Gene ◽  
Genomic Structure ◽  
Receptor Gene ◽  
Mouse Fibroblast ◽  
Noncoding Region ◽  
Receptor Expression ◽  
Coding Region ◽  
Isolation And Characterization ◽  
Interleukin 9

To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5′ noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5′ noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells.

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