The ELAV/Hu protein Found in neurons regulates cytoskeletal and ECM adhesion inputs for space-filling dendrite growth
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ABSTRACT:
PROVIDER: PRJNA671867 | ENA |
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC7793258 | biostudies-literature
Project description:RNA-binding proteins play important roles in neuronal development and function. We sought to understand the role of the RNA-binding protein Found in neurons (Fne) in regulating the development of Drosophila larval class IV dendritic arborization neurons, in part by identifying its transcript targets using TRIBE. We were able to identify many cell adhesion proteins and cytoskeletal regulators as targets of Fne, which is consistent with our genetic and phenotypic analysis of the role of Fne in class IV da neurons.
2020-11-18 | GSE160111 | GEO
Project description:An animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR-14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.
2024-03-31 | GSE262604 | GEO
Project description:We investigated mRNA regulatory proteins of the ELAV family following 10 min global brain ischemia and 8 hrs reperfusion (8R) or non-ischemic controls (NIC) in rat hippocampal CA1 and CA3. There were three main experiments: (1) Shot-gun proteomics of polysome pellets from NIC and 8R CA1 and CA3, (2) Shot-gun proteomics of ELAV immunoprecipitate eluents from NIC and 8R CA1 and CA3, and (3) Proteomics of ELAV antisera-reactive bands excised from nitrocellulose following ELAV Western blot.
2016-07-07 | PXD004078 | Pride
Project description:Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes, such as stem cell differentiation and cancer. A particularly dramatic form of APA has been documented in the developing nervous system of flies and mammals, whereby a variety of neurogenic genes undergo coordinate extension of their 3’ UTRs. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation (poly(A)) sites, thereby fostering the formation of 3’ extensions that can reach 12 kb in length. Here, we present evidence that paused Pol II plays an important role in the selective recruitment of ELAV to elongated genes. Replacing native promoters of elongated genes with heterologous promoters blocks normal 3’ extension in the nervous system, while native promoters can induce 3’ extension in ectopic tissues expressing ELAV. Computational analyses suggest that the promoter regions of elongated genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ELAV ChIP-Seq assays indicate pervasive binding to the promoter regions of extended genes. Our study provides the first evidence for a regulatory link between promoter-proximal pausing and APA. ELAV ChIP-Seq assays were conducted with nuclei obtained from 6-8 hr and 10-12 hr embryos
2014-11-21 | E-GEOD-63323 | biostudies-arrayexpress
Project description:ELAV/Hu factors are conserved RNA binding proteins that play diverse roles in mRNA processing and regulation. The founding member, Drosophila Elav, was recognized as a vital neural factor 35 years ago. Nevertheless, still little is known about its impacts on the transcriptome, and potential functional overlap with its paralogs. Building on our recent findings that neural-specific lengthened 3' UTR isoforms are co-determined by ELAV/Hu factors, we address their impacts on splicing. While only a few splicing targets of Drosophila are known, we find that ectopic expression of the three family members (Elav, Fne and Rbp9) induces overlapping changes to hundreds of cassette exon and dozens of alternative last exon (ALE) splicing events. Reciprocally, double mutants of elav/fne, but not elav alone, have opposite effects on both classes of regulated mRNA processing events in the larval CNS. While manipulation of Drosophila ELAV/Hu factors induces both exon skipping and inclusion, motif analysis indicates their major direct effects are to suppress cassette exon usage. Moreover, the roles of ELAV/HU factors in global promotion of distal ALE splicing are mechanistically linked to terminal 3' UTR extensions in neurons, since both involve local suppression of proximal polyadenylation signals via ELAV/Hu binding sites downstream of cleavage sites. The phenotypic impact of combined ELAV/Hu activities in neural mRNA processing is overt, since fne loss strongly enhances neuronal differentiation phenotypes in elav mutants. Finally, we provide evidence for conservation in mammalian neurons, which undergo broad programs of distal ALE and APA lengthening, linked to ELAV/Hu motifs downstream of regulated polyadenylation sites. Overall, ELAV/Hu proteins orchestrate multiple conserved programs of neuronal mRNA processing by suppressing alternative exons and polyadenylation sites.
2021-02-23 | GSE164129 | GEO
Project description:Patterns of synaptic connectivity are remarkably precise and complex. Single-cell RNA sequencing has revealed a vast transcriptional diversity of neurons. Nevertheless, a clear logic underlying the transcriptional control of neuronal connectivity has yet to emerge. Here, we focused on Drosophila T4/T5 neurons, a class of closely related neuronal subtypes with different wiring patterns. Eight subtypes of T4/T5 neurons are defined by combinations of two patterns of dendritic inputs and four patterns of axonal outputs. Single-cell profiling during development revealed distinct transcriptional programs defining each dendrite and axon wiring pattern. These programs were defined by the expression of a few transcription factors and different combinations of cell surface proteins. Gain and loss of function studies provide evidence for independent control of different wiring features. We propose that modular transcriptional programs for distinct wiring features are assembled in different combinations to generate diverse patterns of neuronal connectivity.
2019-11-05 | GSE126139 | GEO
Project description:Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes, such as stem cell differentiation and cancer. A particularly dramatic form of APA has been documented in the developing nervous system of flies and mammals, whereby a variety of neurogenic genes undergo coordinate extension of their 3’ UTRs. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation (poly(A)) sites, thereby fostering the formation of 3’ extensions that can reach 12 kb in length. Here, we present evidence that paused Pol II plays an important role in the selective recruitment of ELAV to elongated genes. Replacing native promoters of elongated genes with heterologous promoters blocks normal 3’ extension in the nervous system, while native promoters can induce 3’ extension in ectopic tissues expressing ELAV. Computational analyses suggest that the promoter regions of elongated genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ELAV ChIP-Seq assays indicate pervasive binding to the promoter regions of extended genes. Our study provides the first evidence for a regulatory link between promoter-proximal pausing and APA.
2014-11-21 | GSE63323 | GEO
Project description:Three potential ELAV-like proteins of T. brucei, including Tb927.3.2930, Tb927.7.5380, and Tb927.8.6650, were either inhibited by RNAi or phenotypically activated by over-expression, followed by microarray analysis of the transcriptome. The results indicated that these ELAV-like proteins regulate the abundance of a large number of T. brucei transcripts, potentially through regulation of mRNA stability.
2013-04-18 | GSE46161 | GEO
Project description:Three potential ELAV-like proteins of T. brucei, including Tb927.3.2930, Tb927.7.5380, and Tb927.8.6650, were either inhibited by RNAi or phenotypically activated by over-expression, followed by microarray analysis of the transcriptome. The results indicated that these ELAV-like proteins regulate the abundance of a large number of T. brucei transcripts, potentially through regulation of mRNA stability. Each of the three ELAV-like proteins were either inhibited by RNAi or over-expressed, in stable transgenic procyclic form cell lines. Total RNA was extracted 48h after tetracycline induction of the constructs (except for total RNA from Tb927.8.6650 RNAi which was extracted 24h after tet-induction), and sent to NimbleGen for cDNA synthesis and hybridization. Non-induced cells were analyzed in parallel.
2013-04-18 | E-GEOD-46161 | biostudies-arrayexpress