Axon-enriched lincRNA ALAE is required for axon elongation via regulating local mRNA translation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA636646 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11906473_1.fastq.gz | Fastqsanger.gz | |||
| SRR11906473_2.fastq.gz | Fastqsanger.gz | |||
| SRR11906474_1.fastq.gz | Fastqsanger.gz | |||
| SRR11906474_2.fastq.gz | Fastqsanger.gz | |||
| SRR11906475_1.fastq.gz | Fastqsanger.gz |
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Project description:Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. To seek the axon-enriched lincRNAs in DRG neurons, we performed high-throughput RNA-seq of cultured rat dorsal root ganglion (DRG) neurons at P0 to profile lincRNAs. Profiling of highly expressed lincRNAs in RNA-seq and their enrichment in the axon of DRG neurons. We report a previously unappreciated axon-enriched lincRNA regulating axon elongation, thus referred to as ALAE. ALAE functionally associates with KHSRP for preventing KHSRP binding on Gap43 mRNA, thereby maintaining GAP43 synthesis and facilitating axon elongation.
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Project description:Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. Here, we report a previously unappreciated axon-enriched lincRNA regulating axon elongation, thus referred to as ALAE. Profiling of highly expressed lincRNAs detected abundant and enriched ALAE in the axon of dorsal root ganglion (DRG) neurons, where it locally promoted axon elongation. Mechanically, ALAE directly interacted with the KH3-4 domains of KH-type splicing regulatory protein (KHSRP) and impeded its association with growth-associated protein 43 (Gap43) mRNA.We used MS to identify proteins interacting with ALAE by combining with RNA pull down assay.
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Project description:During brain wiring, mRNAs are trafficked into axons and growth cones where they are differentially translated in response to extrinsic signals. Differential control of local protein synthesis mediates neuronal compartment-specific behaviors that aid axon guidance. Yet little is understood about how specific mRNAs are selected for translation. Here we have investigated the local role of microRNAs (miRNAs) in mRNA-specific translation during axon pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons. Profiling experiments revealed a rich repertoire of axonal miRNAs in developing RGC axons and identified miR-182 as one of the most abundant. Loss of miR182 impairs Slit2-induced growth cone repulsion and causes RGC axon targeting defects in vivo. To aid miRNA target prediction, we also profiled mRNA expression in RGC axons. Our results show that miR-182 targets cofilin1 mRNA in RGC growth cones and modulates its local translation in response to Slit2.
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Project description:The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol and in axons of motoneurons, and that depletion of Ptbp2 affects axon growth. We identified Ptbp2 as a major interactor of the 3' UTR of Hnrnpr mRNA. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus, suggest a mechanism whereby Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.
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