Transcriptome profiling of untreated and doxycycline-treated HeLa/TO-SmN
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Chin Li
PROVIDER: E-GEOD-54136 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Muscular atrophy (SMA) is an autosomal recessive disease causing selective motor neuron death by the loss of telomeric survival motor neuron gene, SMN1. Axonal SMN, a-SMN, is a truncated form of SMN, derived from an alternatively spliced SMN1 gene. (Setola, et. al. 2007 PNAS 104, 1959-1964). The cellular clones expressing a-SMN in a tetracycline-dependent manner were isolated from NSC34 by two-step stable transfection, first with the tetracycline-repressor construct and subsequently with the a-SMN cDNA. To identify novel a-SMN target genes, the transcriptome of several a-SMN clones was analyzed and compared with that of parental cells.
2012-01-07 | E-MEXP-3402 | biostudies-arrayexpress
Project description:Purpose is to examine the effect of SmN expression to gene expression in HeLa
2015-01-16 | GSE54136 | GEO
Project description:Although recent advances in gene therapy provide hope for spinal muscular atrophy (SMA) patients, the pathology remains the leading genetic cause of infant mortality. SMA is a monogenic pathology that originates from the loss of the SMN1 gene in most cases or mutations in rare cases. Interestingly, SMN1 mutations occur broadly either within the TUDOR methyl-arginine (Rme) reader domain of SMN or its carboxy terminal oligomerization domain. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a proximity-dependent biotinylation proteomic (BioID) approach, we have identified and validated a number of SMN-interacting proteins, including Fragile X mental retardation family members (FMRFM), such as FMRP itself as well as FXR1 and FXR2, some depending on a wild-type version of the TUDOR domain.
2022-10-19 | PXD030970 | Pride
Project description:The C-terminal domain (CTD) of the RNA polymerase II (RNAPII) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodeling. Here, we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires Protein Arginine Methyltransferase 5 (PRMT5) and recruits the Tudor domain of the Survival of Motor Neuron (SMN) protein, which is mutated in spinal muscular atrophy (SMA). SMN interacts with Senataxin, which is sometimes mutated in Ataxia Oculomotor Apraxia 2 (AOA2) and Amyotrophic Lateral Sclerosis (ALS4). Because R1810me2s and SMN, like Senataxin, are required for resolving RNA-DNA hybrids, created by RNA polymerase II, that form â??R-loopsâ?? in transcription termination regions, we propose that R1810me2s, SMN, and Senataxin are components of a pathway for R-loop resolution in which defects can influence transcription termination and may contribute to neurodegenerative disorders. ChIP of RNAPII in Raji cells expressing shRNG against SMN or GFP; ChIP against RNAPII in Raji cells where endogenous RNAPII has been replaced with wt or R1810A mutant amanitin-resistant protein; and ChIP of SMN in HEK293 cells.
2015-12-31 | E-GEOD-73379 | biostudies-arrayexpress
Project description:Transcriptiome profiling of SMN MO injected, Gemin2 MO injected zebrafish embryos vs Control MO injected Two condition experiment : MO injected vs control. Biological replicates for SMN MO injected : 6, Biological replicates for Gemin2 MO injected: 7; Control MO injected from 6 independent batches pooled to serve as common control sample in all arrays.
2013-12-05 | E-GEOD-47001 | biostudies-arrayexpress
Project description:Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and SmB, a member of the Sm family of snRNP-associated proteins, in neural cells. By comparing the interactomes of SmB and SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN may have potential as a therapeutic target for SMA together with, or in place of, those targeting SMN expression
2018-03-15 | PXD008710 | Pride
Project description:Several studies indicate that SMN-containing mRNP complexes could be involved in the axonal localization of a large number of mRNAs. We have used murine motor neuron-like NSC-34 cells and RNA Immuno-Precipitation experiments coupled to microarray analyses to perform a genome-wide analysis of RNA species present in mRNP complexes containing the full length SMN protein (flSMN). In situ hybridization and immuno-fluorescence experiments performed on several candidates indicate that these mRNAs colocalize with the SMN protein in neurites and axons of differentiated NSC-34 cells. Moreover, they localize in cell processes in a SMN-dependent manner. Thus, low SMN levels might result in localization deficiencies of mRNAs required for axonogenesis. RNA species coimmunoprecipitated with the SMN protein were used for hybridization of Affymetrix microarrays
2013-11-29 | E-GEOD-40197 | biostudies-arrayexpress
Project description:Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq In total 12 samples were analyzed, divided into four distinct groups (treated with SMN-C3 @ 500 nM; controls for SMN-C3; treated with SMN-C1 @ 100 nM; controls for SMN-C1) containing 3 replicates each.
2014-10-22 | E-GEOD-62540 | biostudies-arrayexpress
Project description:Molecular chaperones and co-chaperones are highly conserved cellular components that perform variety of duties related to the proper three-dimensional folding of the proteome. The Survival Motor Neuron (SMN) complex is an RNP assembly chaperone and serves as a paradigm for studying how specific small nuclear (sn)RNAs are identified and paired with their client substrate proteins. SMN forms the oligomeric core of this complex, and missense mutations in its YG box self-interaction domain are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood. Given the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. Here, we carried out affinity purification mass spectrometry (AP-MS) of SMN using stable fly lines exclusively expressing either wildtype or SMA-causing missense alleles. Bioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones.
2024-09-11 | PXD053506 | Pride
Project description:The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease ALS, is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and reduce interaction with U1-snRNP. Correspondingly, global RNA analysis reveals a mutant-dependent loss of splicing activity, with ALS-linked mutants failing to reverse changes caused by loss of wild-type FUS/TLS. Furthermore, a common FUS/TLS mutant-associated RNA splicing signature is identified in ALS patient fibroblasts. Taken together, our studies establish potentially converging disease mechanisms in ALS and spinal muscular atrophy, with ALS-causative mutants acquiring properties representing both gain (dysregulation of SMN) and loss (reduced RNA processing mediated by U1-snRNP) of function. RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Generation sequencing (RASL-seq) method was used for analyzing alternative splicing changes. Oligonucleotide probes are designed to anneal to the exon-exon junctions. The probe library was assembled to assess 5530 unique alternative splicing events, most of which were exon inclusion or skipping, with a minority for alternative 5’- or 3’- splice sites. The splicing changes were compared among groups of reducing FUS/TLS or SMN levels, or expressing various FUS mutations to determine the loss versus gain of FUS/TLS function on splicing regulation.
2015-02-10 | E-GEOD-64078 | biostudies-arrayexpress