Cytoplasmic long non-coding RNAs are differentially regulated and translated during human neuronal differentiation
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ABSTRACT:
PROVIDER: PRJNA699598 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14760769.fastq.gz | Fastqsanger.gz | |||
| SRR14760770.fastq.gz | Fastqsanger.gz | |||
| SRR14760771.fastq.gz | Fastqsanger.gz | |||
| SRR14760772.fastq.gz | Fastqsanger.gz | |||
| SRR14760773.fastq.gz | Fastqsanger.gz |
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Project description:The expression of long non-coding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SH5Y cells. We discovered 237 cytoplasmic lncRNAs upregulated during early neuronal differentiation, 58-70% of which are associated with polysome translation complexes. Amongst these polysome associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. 15/45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea suggesting they are under strong selective constraint in this clade. Profiling of publicly available datasets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localises to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a non-canonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.
2021-07-16 | GSE166214 | GEO
Project description:The expression of long noncoding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SY5Y cells. We discovered 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, 58%-70% of which are associated with polysome translation complexes. Among these polysome-associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. Fifteen of 45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea, suggesting they are under strong selective constraint in this clade. The profiling of publicly available data sets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development, and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localizes to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells, indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a noncanonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.
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Project description:Differentially expressed and translated genes regulated by PM2.5 exposure in BEAS-2B cells
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Project description:Next Generation Sequencing identifies differentially translated genes regulated by PM2.5 exposure in BEAS-2B cells [Ribo-seq]
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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived frontal cortex transcriptome profiling (RNA-seq) from control and a mouse of ALS-FUS. Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS, lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, including locomotor hyperactivity and alterations in social interactions, in the absence of widespread neuronal loss. Mechanistically, we identified a profound increase in neuronal activity in the frontal cortex of Fus knock-in mice in vivo. Importantly, RNAseq analysis suggested involvement of defects in inhibitory neurons, that was confirmed by ultrastructural and morphological defects of inhibitory synapses and increased synaptosomal levels of mRNAs involved in inhibitory neurotransmission. Thus, cytoplasmic FUS triggers inhibitory synaptic deficits, leading to increased neuronal activity and behavioral phenotypes. FUS mislocalization may trigger deleterious phenotypes beyond motor neuron impairment in ALS, but also in other neurodegenerative diseases with FUS mislocalization.
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Project description:Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Although most eukaryotic mRNAs need a functional cap binding complex eIF4F for efficient 5' end-dependent scanning to initiate translation, picornaviral, hepatitis C viral, and a few cellular RNAs have been shown to be translated by internal ribosome entry, a mechanism that can operate in the presence of low levels of functional eIF4F. To identify cellular mRNAs that can be translated when eIF4F is depleted or in low abundance and that, therefore, may contain internal ribosome entry sites, mRNAs that remained associated with polysomes were isolated from human cells after infection with poliovirus and were identified by using a cDNA microarray. Approximately 200 of the 7000 mRNAs analyzed remained associated with polysomes under these conditions. Among the gene products encoded by these polysome-associated mRNAs were immediate-early transcription factors, kinases, and phosphatases of the mitogen-activated protein kinase pathways and several protooncogenes, including c-myc and Pim-1. In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly. Subsequent tests confirmed the presence of internal ribosome entry sites in the 5' noncoding regions of both Cyr61 and Pim-1 mRNAs. Overall, this study suggests that diverse mRNAs whose gene products have been implicated in a variety of stress responses, including inflammation, angiogenesis, and the response to serum, can use translational initiation mechanisms that require little or no intact cap binding protein complex eIF4F. This study is described more fully in Johannes G et al.(1999) Proc Natl Acad Sci U S A 96:13118-23.
2002-06-27 | E-GEOD-62 | biostudies-arrayexpress
Project description:SYNCRIP, a member of the cellular heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA binding proteins, regulates various aspects of neuronal development and plasticity. Although SYNCRIP has been identified as a component of cytoplasmic RNA granules in dendrites of mammalian neurons, only little is known about the specific SYNCRIP target mRNAs that mediate its effect on neuronal morphogenesis and function. Here, we present a comprehensive characterization of the cytoplasmic SYNCRIP mRNA interactome using iCLIP in primary rat cortical neurons. We identify hundreds of bona fide SYNCRIP target mRNAs, many of which encode for proteins involved in neurogenesis, neuronal migration and neurite outgrowth. From our analysis, the stabilization of mRNAs encoding for components of the microtubule network, such as doublecortin (Dcx), emerges as a novel mechanism of SYNCRIP function in addition to the previously reported control of actin dynamics. Furthermore, we found that SYNCRIP interacts with miRISC and synergizes with pro-neural miRNAs, such as miR-9. Based on our findings, we propose a model whereby SYNCRIP promotes early neuronal differentiation by a two-tier mechanism involving the stabilization of pro-neural mRNAs by direct 3’UTR interaction and the repression of anti-neural mRNAs in a complex with neuronal miRISC. Together, our findings provide a rationale for future studies investigating the function of SYNCRIP in mammalian brain development and disease.
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Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from RNA-seq experiments. We performed RNA-seq to profile gene expression and splicing changes. The expression levels of Rbfox1 and Rbfox3 in cultured mouse hippocampal neurons were reduced by siRNAs. The reduction of Rbfox1 and 3 was rescued by expression of cytoplasmic or nuclear Rbfox1 splice isoform. The gene expression and splicing profiles were compared between different treatments. Eight samples were analyzed.
2015-12-10 | E-GEOD-71916 | biostudies-arrayexpress