Similar Datasets
Project description:Regulation of RNA localization by FMR1
| PRJNA573700 | ENA
Project description:Subcellular RNA localization during Drosophila embryonic neurogenesis [fractionation-Seq]
| PRJNA415601 | ENA
Project description:We isolated whole embryo, nuclear, and cytoplasmic lysates from Drosophila embryos during early and late embryogenesis In Drosophila melanogaster, cell-type specification during early nervous system development requires precise regulation of gene expression in time and space. To investigate the gene regulation patterns in early neuronal development, we developed a method 'DIV-SortSeq' to enrich for specific neuroglial cell types for RNA sequencing: from early columnar subdivision and specification, through neuroglial differentiation. DIV-SortSeq recapitulates many of the known protein-coding transcriptome dynamics, as well as novel transcriptional regulatory patterns. We also performed nuclear-cytoplasmic fractionation of whole embryos - Fractionation-Seq - to assess temporal changes in subcellular localization of transcripts during embryogenesis. We present these data as a resource to permit further in-depth investigation into the functional roles of the coding and noncoding transcriptome during early Drosophila neurogenesis.
2019-02-19 | GSE106094 | GEO
Project description:The Muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in Myotonic Dystrophy (DM), where expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts using RNA sequencing and crosslinking/immunoprecipitation-sequencing approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function, in a pattern indicative of functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of sub-cellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs encoding membrane, synaptic and other proteins in both mouse and Drosophila cells, and Mbnls also contribute to protein secretion. These findings hold several new implications for DM pathogenesis. To assess global functions of Muscleblind proteins, RNA-Seq was performed using WT and Mbnl1 KO brain, heart, and muscle (5 mice each). Additionally, C2C12 mouse myoblasts were depleted of Mbnl1, Mbnl2, or both. Subcellular fractionation experiments were performed to analyze mRNA localization following depletion of Mbnl1 and Mbnl2 in C2C12 mouse myoblasts, and following depletion of Mbnl in Drosophila S-2R+ cells. CLIP-Seq was also performed against Mbnl1 in mouse brain, heart, muscle, and C2C12 myoblasts. Finally, ribosome footprinting was performed with C2C12 mouse myoblasts that were depleted of Mbnl1, Mbnl2, or both.
2012-08-17 | E-GEOD-39911 | biostudies-arrayexpress
Project description:Neurodegeneration-associated mutations affect the dynamics of transient cytoplasmic stress granule (SG). However, it is unclear if and how aberrant SG behavior is linked to the downstream formation of protein aggregates and other molecular defects that persist after stress subsides. Using subcellular fractionation combined with RNA-seq (CeFra-seq) we characterize the global mRNA localization landscape in human pluripotent stem cell-derived motor neuron (PS-MN). Using CeFra-seq and quantitative proteomics, we find that transient stress leads to a widespread reshaping of mRNA and protein localization that recapitulates key molecular phenotypes of Amyotrophic Lateral Sclerosis (ALS). While the substantial reorganization of the global mRNA localization landscape is largely reversible in wild type PS-MNs, we find that cells harboring ALS-linked mutations in HNRNPA2B1 are unable to recover and display a delayed-onset increase in neuronal cell death in response to stress. Our findings reaffirm the importance of stress-induced molecular mechanisms in the formation of molecular disease pathology of ALS and highlight the importance of targeting SG-relevant molecular mechanisms in the development of therapeutic strategies.
2021-08-01 | GSE157467 | GEO
Project description:m6A and YTHDF proteins control the subcellular localization of select neuronal mRNAs
| PRJNA799732 | ENA
Project description:Using cell-free fetal RNA from amniotic fluid supernatant samples, the gene expression profiles of fetuses with varying FMR1 5’ UTR CGG repeat lengths were compared to gestational age- and sex-matched controls. Broad patterns of genome-wide expression changes were identified when comparing fetuses with expanded FMR1 alleles to those with normal length FMR1 alleles. Genes with altered expression include those related to ubiquitination, mitochondrial function and neuronal/synaptic architecture as well as genes previously linked to other intellectual disabilities and abnormalities of motor function.
2016-09-01 | GSE83556 | GEO
Project description:Analysis of subcellular location of mitochondrial gene products using two distinct cell fractions: membrane-bound (MB) and high speed (HS) obtained via biochemical fractionation from wild type individuals and mia40a zebrafish mutants, respectively.
2022-10-19 | GSE167587 | GEO
Project description:The transport of mRNAs to distal subcellular compartments is an important component of spatial gene expression control in neurons. However, the mechanisms that control mRNA localization in neurons are not completely understood. Here, we identify the abundant base modification, m6A, as a regulator of mRNA localization in neurons. Transcriptome-wide analysis of mRNA localization in neurons following genetic loss of m6A reveals hundreds of transcripts that exhibit altered subcellular localization. Additionally, using a reporter system, we show that mutation of specific m6A sites in select neuronal transcripts diminishes their localization to neurites. Single molecule fluorescent in situ hybridization experiments further confirm our findings and identify the m6A reader proteins YTHDF2 and YTHDF3 as mediators of this effect. Our findings reveal a novel function for m6A in controlling mRNA localization in neurons and enable a better understanding of the mechanisms through which m6A influences gene expression in the brain.
2022-04-26 | GSE171199 | GEO
Project description:Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In non-neuronal cells, a subset of mRNAs localize to cell protrusions and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C protein abundance, distribution, οr ability to traffic other mRNAs. Conversely, robust Kif1c mRNA localization is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mis-localization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein-protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle used by protrusion-enriched mRNAs in non-neuronal cells.
2023-02-24 | GSE219089 | GEO