Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [Ribo-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1129445 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29638112.fastq.gz | Fastqsanger.gz | |||
| SRR29638113.fastq.gz | Fastqsanger.gz | |||
| SRR29638114.fastq.gz | Fastqsanger.gz | |||
| SRR29638115.fastq.gz | Fastqsanger.gz | |||
| SRR29638116.fastq.gz | Fastqsanger.gz |
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Project description:Singular olfactory receptor (OR) expression is critical for vertebrate olfaction because the sequence of the chosen OR protein determines both the receptive field and axon guidance properties of each olfactory sensory neuron (OSN). However, numerous single cell RNA-seq studies reveal that OSN progenitors co-transcribe seemingly random combinations of OR genes before a gradual transition to transcriptional singularity. Here, we show that MEX3A, a RING and KH domain protein expressed during polygenic OR transcription, prevents efficient OR protein expression before the emergence of a prevalent, transcriptionally dominant OR allele. Consequently, MEX3A deletion enhances OR mRNA and OR protein abundance in OSN progenitors, resulting in premature induction of Perk signaling, biased OR gene choice, and OSN axon mistargeting. Our experiments uncover a novel, post-transcriptional mechanism of OR gene regulation that assures that the identity of the expressed OR can influence the identity of the OSN only at the onset of singular OR choice.
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Project description:Singular olfactory receptor (OR) expression is critical for vertebrate olfaction because the sequence of the chosen OR protein determines both the receptive field and axon guidance properties of each olfactory sensory neuron (OSN). However, numerous single cell RNA-seq studies reveal that OSN progenitors co-transcribe seemingly random combinations of OR genes before a gradual transition to transcriptional singularity. Here, we show that MEX3A, a RING and KH domain protein expressed during polygenic OR transcription, prevents efficient OR protein expression before the emergence of a prevalent, transcriptionally dominant OR allele. Consequently, MEX3A deletion enhances OR mRNA and OR protein abundance in OSN progenitors, resulting in premature induction of Perk signaling, biased OR gene choice, and OSN axon mistargeting. Our experiments uncover a novel, post-transcriptional mechanism of OR gene regulation that assures that the identity of the expressed OR can influence the identity of the OSN only at the onset of singular OR choice.
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Project description:Singular olfactory receptor (OR) expression is critical for vertebrate olfaction because the sequence of the chosen OR protein determines both the receptive field and axon guidance properties of each olfactory sensory neuron (OSN). However, numerous single cell RNA-seq studies reveal that OSN progenitors co-transcribe seemingly random combinations of OR genes before a gradual transition to transcriptional singularity. Here, we show that MEX3A, a RING and KH domain protein expressed during polygenic OR transcription, prevents efficient OR protein expression before the emergence of a prevalent, transcriptionally dominant OR allele. Consequently, MEX3A deletion enhances OR mRNA and OR protein abundance in OSN progenitors, resulting in premature induction of Perk signaling, biased OR gene choice, and OSN axon mistargeting. Our experiments uncover a novel, post-transcriptional mechanism of OR gene regulation that assures that the identity of the expressed OR can influence the identity of the OSN only at the onset of singular OR choice.
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Project description:Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [scRNA-Seq]
| PRJNA1129446 | ENA
Project description:Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [RNA-Seq]
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Project description:We have discovered subsets of axon guidance molecules and transcription factors that are enriched in specific subsets of olfactory sensory neurons. We have demonstrated guidance activity for three of the candidate axon guidance genes we identified, suggesting that this approach is an efficient method for characterizing guidance systems relevant to olfactory axon targeting.
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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis
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Project description:Using the highly sensitive miRNA array, we screened 40 microRNAs abundant in the olfactory bulb and we explored the functions of these miRNAs in the olfactory bulb by Gene Ontology and Kyoto Encyclopedia of Genes annotation. The enrichment results indicated that these miRNAs mainly participated in the axon guidance process. Furthermore, the quantitative real-time polymerase chain reaction, immunohistochemistry, and dual luciferase reporter assay results showed that miR-30c is a specific regulator of semaphorin-3A, which will give new insights in disclosing the mechanism of functional maintenance and sexual-specific differentiation of the olfactory bulb. In this study, three samples from steady-state mice were used to acquire the miRNA expression profiling and the function of the abudant miRNAs in the olfactory bulb were analyzed by bioinformatic methods.Finally, miR-30c was experimentally validated to be a regulator of semaphorin-3A, an important axon guidance cue in the nervous system.
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