RNA-binding protein Syncrip regulates Starvation-Induced Hyperactivity in adult Drosophila
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ABSTRACT:
PROVIDER: PRJNA630161 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11684039_1.fastq.gz | Fastqsanger.gz | |||
| SRR11684039_2.fastq.gz | Fastqsanger.gz | |||
| SRR11684040_1.fastq.gz | Fastqsanger.gz | |||
| SRR11684040_2.fastq.gz | Fastqsanger.gz | |||
| SRR11684041_1.fastq.gz | Fastqsanger.gz |
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Project description:How to respond to starvation determines fitness. One prominent behavioral response is increased locomotor activities upon starvation, also known as Starvation-Induced Hyperactivity (SIH). SIH is paradoxical as it promotes food seeking but also increases energy expenditure. Despite its importance in regulating fitness, the genetic contributions to SIH as a behavioral trait remains unexplored. Here, we examined SIH in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association studies. We identified 27 significant loci, corresponding to 18 genes, significantly associated with SIH in adult Drosophila. Gene enrichment analyses indicated that genes encoding ion channels and mRNA binding proteins (RBPs) were most enriched in SIH. We are especially interested in RBPs because they provide a potential mechanism to quickly change protein expression in response to environmental challenges. Using RNA interference, we validated the role of Syp in regulating SIH. Syp encodes Syncrip, an RBP. While ubiquitous knockdown of Syp led to lethality during development, adult flies with neuron specific Syp knockdown were viable and exhibited decreased SIH. Using the Temporal and Regional Gene Expression Targeting (TARGET) system, we further confirmed the role of Syp in adult neurons in regulating SIH. Lastly, RNA-seq analyses revealed that Syp was alternatively spliced under starvation while its expression level was unchanged. Together, this study not only demonstrates genetic contributions to SIH as an important behavioral trait but also highlights the significance of RBPs and post-transcriptional processes in regulating SIH.
2020-07-20 | GSE149790 | GEO
Project description:How to respond to starvation determines fitness. One prominent behavioral response is increased locomotor activities upon starvation, also known as Starvation-Induced Hyperactivity (SIH). SIH is paradoxical as it promotes food seeking but also increases energy expenditure. Despite its importance in fitness, the genetic contributions to SIH as a behavioral trait remains unexplored. Here, we examined SIH in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association studies. We identified 23 significant loci, corresponding to 14 genes, significantly associated with SIH in adult Drosophila. Gene enrichment analyses indicated that genes encoding ion channels and mRNA binding proteins (RBPs) were most enriched in SIH. We are especially interested in RBPs because they provide a potential mechanism to quickly change protein expression in response to environmental challenges. Using RNA interference, we validated the role of syp in regulating SIH. syp encodes Syncrip (Syp), an RBP. While ubiquitous knockdown of syp led to semi-lethality in adult flies, adult flies with neuron-specific syp knockdown were viable and exhibited decreased SIH. Using the Temporal and Regional Gene Expression Targeting (TARGET) system, we further confirmed the role of Syp in adult neurons in regulating SIH. To determine how syp is regulated by starvation, we performed RNA-seq using the heads of flies maintained under either food or starvation conditions. RNA-seq analyses revealed that syp was alternatively spliced under starvation while its expression level was unchanged. We further generated an alternatively-spliced-exon-specific knockout (KO) line and found that KO flies showed reduced SIH. Together, this study demonstrates a significant genetic contribution to SIH as a behavioral trait, identifies syp as a SIH gene, and highlights the significance of RBPs and post-transcriptional processes in the brain in regulating behavioral responses to starvation.
| S-EPMC7932510 | biostudies-literature
Project description:RNA binding proteins (RBPs) tightly control mRNA abundance, stability and translation while mutations or altered expression of specific factors can drive malignancy1,2. However, the identity of the RBPs that govern cancer stem cell self-renewal remains poorly characterized. The MSI2 RBP is a central regulator of translation of the cancer stem cell program3-5,6. Here we report, through proteomics analysis of the MSI2 interacting RBP network and functional shRNA screening, 24 genes required for in vivo leukemia, 20 of which are direct MSI2 protein interactors. Seven of these shRNA screen hits were retested in vitro and found to be required for myeloid colony formation. SYNCRIP (also known as HNRP-Q or NSAP1) was the most differentially required gene between normal (c-kit enriched cells) and myeloid leukemia cells. SYNCRIP is highly expressed in mouse and human leukemia cells and its depletion increases apoptosis, differentiation and delays leukemogenesis. Gene expression profiling of SYNCRIP depleted cells demonstrates a loss of the MLL-AF9 and HOXA9 leukemia stem cell gene associated program. SYNCRIP interacts with MSI2 indirectly through shared mRNA targets (such as Hoxa9, Myc and Ikzf2) and MSI2 or HOXA9 overexpression rescues the effects of SYNCRIP depletion. Strikingly, the shRNA-SYNCRIP gene expression signature can predict survival in AML patients. Overall, we uncovered a functionally dysregulated riboproteome in cancer that can be further distinguished from normal cells and propose that targeting this network could result in a novel therapeutic strategy in eradicating cancer stem cells.
2017-04-24 | GSE74178 | GEO
Project description:RNA binding protein SYNCRIP regulates the leukemia stem cell program
| PRJNA301179 | ENA
Project description:Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is often deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vescicles are still poorly understood. We identified here the RNA binding protein SYNCRIP (Synaptotagmin-binding Cytoplasmic RNA-Interacting Protein, also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP was found to bind directly a subset of miRNAs enriched in exosomes, sharing a common extra-seed sequence that we named hEXO motif. In vivo knock-down of SYNCRIP impaired microRNA sorting in exosomes and the hEXO motif was proven to play a role in the regulation of miRNA localization, as its embedment into a poorly exported miRNA enhanced its loading into exosomes. These results provide a new insight in the mechanisms of miRNA exosomal sorting process, that ca be exploited to further understand the role of these extracellular vescicles in cell-to-cell communications and the control of tissue micoenvironments.
2016-09-02 | E-MTAB-4502 | 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.
2021-05-05 | GSE149561 | GEO
Project description:SYNCRIP depletion results in HSCs losing their self renewal abilities. Single cell sequencing was conducted in SYNCRIP WT and KO bone marrow LK (lineage -, cKit+) cells to decipher the effect of Syncrip deletion on cellular identities along the hematopoietic hierarchy, and to gain an in-depth assessment of the transcriptomic changes in different cell types upon SYNCRIP loss.
2023-03-01 | GSE202421 | GEO
Project description:Identifying SYNCRIP RNA-binding targets in HSC and MPP populations, in order to uncover which direct targets influence SYNCRIP's role in maintaining HSCs self renewal capacity.
2023-03-01 | GSE202464 | GEO
Project description:Alterations in SYNCRIP activity were found to alter gene transcription in leukemia cells. The effects of transcription alterations on expression of the corresponding proteins were investigated by LC/MSMS
2023-05-10 | PXD019779 | Pride
Project description:T cell activation leads to dramatic changes in cellular phenotype. We used CD3/CD28-activated human CD4 T cells to study how RNA binding proteins define the post-transcriptional landscape. Using RIPseq, we identified the RNA interactome of U2AF2 and show at the global level that U2AF2 binds the majority of transcripts that are differentially expressed and/or alternatively spliced during CD4 T cell activation. A unique protein interactome centered on U2AF2 is assembled in response to activation. Knocking down specific U2AF2 interacting partners (U2AF1, SYNCRIP, SRRM2, ILF2) selectively affects cytokine secretion and expression of activation markers. Furthermore, the expression and/or alternative splicing of transcripts important for immune cell function are also affected by knocking down these U2AF2 interacting proteins. U2AF1 and SYNCRIP knockdowns affect the proteins and transcripts bound to U2AF2, altering the transcriptome. Our work highlights the importance of RNA binding protein complexes in regulating the differential expression and alternative splicing that defines T cell activation. HTA 2.0 microarray results of U2AF2 RIP RNA from a primary CD4 T cell culture after treatment with siRNAs (Control, U2AF1, and SYNCRIP) and 24 hours after anti-CD3/CD28 bead activation Please note that the Series supplementary 'U2AF2RIP_HTA2_all_siRNA_100414.xlsx' file includes multiple worksheets containing: 1) Differentially expressed genes in ctrl siRNA vs. U2AF1 siRNA; 2) Differntially spliced genes in ctrl siRNA vs. U2AF1 siRNA; 3) Differentially spliced exons in ctrl siRNA vs. U2AF1 siRNA; 4) Differentially expressed genes in ctrl siRNA vs. SYNCRIP siRNA; 5) Differntially spliced genes in ctrl siRNA vs. SYNCRIP siRNA; 6) Differentially spliced exons in ctrl siRNA vs. SYNCRIP siRNA
2015-11-04 | E-GEOD-62922 | biostudies-arrayexpress