Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171399 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR527727.fastq.gz | Fastqsanger.gz | |||
| SRR527728.fastq.gz | Fastqsanger.gz | |||
| SRR527729.fastq.gz | Fastqsanger.gz | |||
| SRR527730.fastq.gz | Fastqsanger.gz | |||
| SRR527731.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:FMR1 targets distinct mRNA sequence elements to regulate protein expression [Affymetrix]
| PRJNA170994 | ENA
Project description:FMR1 targets distinct mRNA sequence elements to regulate protein expression [PAR-CLIP]
| PRJNA171396 | ENA
Project description:Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders. The mRNA profile of RNA recovered from FLAG-antibody immunoprecipitated FMRP was compared to the mRNA profile of the starting lysate material.
2012-12-13 | E-GEOD-39504 | biostudies-arrayexpress
Project description:Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders. PAR-CLIP profiling for wild-type and I304N mutant FMRP isoforms as well as paralogs, FXR1 and FXR2.
2012-12-13 | E-GEOD-39682 | biostudies-arrayexpress
Project description:Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders.
2012-12-13 | GSE39682 | GEO
Project description:Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders.
2012-12-13 | GSE39504 | GEO
Project description:Post-transcriptional gene regulation controls the amount of a protein produced from an individual mRNA transcript by altering mRNA decay and translation rates. Many putative post-transcriptional cis-regulatory elements have been identified from computational, molecular biology, and biochemical studies studies; however, identifying which sequence elements are sufficient to regulate expression remains challenging. We created a high-throughput, cell-based screen that tested the post-transcriptional regulatory potential for thousands of short sequence elements. Sequences with known effects have the expected performance in this screen, showing this methodology is robust. Hundreds of novel short sequences were identified as being able to alter gene expression, both by increasing and decreasing protein production from the fluorescence reporter, and we validated the effects for fifty of these sequences. Importantly, sequences discovered in this screen are conserved in human 3′UTRs, and furthermore, the sequences can regulate expression in the context of those endogenous 3′UTRs. Hundreds of previously unknown post-transcriptional cis-regulatory elements exist, many of which increase gene expression. These results suggest that each human 3′UTR has many small cis-regulatory elements that interact with RNA binding proteins, and these interactions control the fate of an mRNA transcript.
2016-03-07 | GSE75136 | GEO
Project description:The Fragile X Mental Retardation Protein, FMRP, is thought to regulate the translation of a specific set of neuronal mRNAs on polyribosomes. Therefore, we prepared polyribosomes on sucrose gradients and purified mRNA specifically from these fractions, as well as the total mRNA levels, to determine whether a set of mRNAs might be changed in its % association with polyribosomes in the absence of FMRP in the KO mouse model. No significant differences were found, other than the Fmr1 transcript itself, in total mRNA levels or % polyribosome association that withstood multiple test correction, in P7 Fmr1 KO mouse cerebral cortex compared with WT littermates.. We prepared polyribosomes on sucrose gradients from 6 littermate pairs of Fmr1 KO and WT littermates (FVB background, P7 males, cerebral cortex) and purified RNA from both polyribosomal fractions and input to the gradient, reflecting total mRNA levels for comparison.
2011-07-20 | E-GEOD-26745 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) modification of mRNA is emerging as a vital mechanism regulating RNA function. Here, we show that fragile X mental retardation protein (FMRP), an RNA-binding protein, reads m6A to regulate nuclear export of methylated mRNA targets during neural stem cell differentiation. In Fmr1 KO mice neural progenitors show delayed cell cycle exit and differentiation, resulting in their progressive accumulation in the ventricular and subventricular zones. RNA-seq of neural precursor cells (NPCs) from Fmr1 KO mice and m6A-seq uncovered nuclear retention of m6A-modified FMRP target mRNAs involved in regulating neural differentiation, including components of Notch and Hedgehog signaling pathways. Analysis of NPCs from Mettl14 cKO mice, which are devoid of m6A, revealed that methylation of RNAs promotes their nuclear export through CRM1. Altogether, our findings suggest that FMRP reads and facilitates nuclear export of m6A-modified mRNAs to regulate neural stem cell differentiation, contributing to Fragile X syndrome.
2019-07-23 | GSE121809 | GEO
Project description:Fragile X syndrome (FXS) is a neuro-developmental disorder caused by silencing Fmr1, which encodes the RNA-binding protein FMRP. Although Fmr1 is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss of Fmr1 in models of FXS. We have used the precision of Drosophila genetics to test if Fmr1 acutely affects adult neuronal plasticity in vivo, focusing on the s-LNv circadian pacemaker neurons that show 24-hour rhythms in structural plasticity. We found that over-expressing Fmr1 for only 4 hours blocks the activity-dependent expansion of s-LNv projections without altering the circadian clock or activity-regulated gene expression. Conversely, reducing Fmr1 expression prevented retraction of s-LNv projections. One FMRP target we identified in s-LNvs is sif, which encodes a Rac1 GEF. Our data indicate that FMRP normally reduces sif mRNA translation at dusk to lower Rac1 activity and acutely regulate neuronal plasticity.
2025-03-15 | GSE241810 | GEO