CLIPSEQ_CELF1_hsHeLa
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB12208 | ENA |
REPOSITORIES: ENA
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Project description:Myotonic dystrophy type 1 (DM1) is caused by the nuclear accumulation of mutant DMPK mRNA containing CUG-repeat expansions, resulting in a trans-dominant effect on RNA processing by sequestration of MBNL1 and activation of CELF1 splicing regulators. Here, we present a comprehensive study of the MBNL1 and CELF1-regulated splicing in the HeLa cell line that may participate in the complex phenotype of the DM1 disease. We have performed human GeneChip Exon array experiments with RNAs extracted from HeLa cells in which MBNL1 or CELF1 were silenced or over-expressed. MBNL1 or CELF1-silenced HeLa cells showed changes in the expression of 170 probe sets (150 genes) and 893 probe sets (613 genes), whereas MBNL1 or CELF1 over-expression on these cells had 812 probe sets (589 genes) and 684 probe sets (531 genes) altered, respectively. In MBNL1-silenced cells we have found and validated by RT-qPCR the exclusion of RASIP1 exon 4 and of KIF13A exon 26 and the inclusion of MBNL2 exon 5. Furthermore, we have found exclusion of LCOR exon 6 and PIP4K2C exon 1, and inclusion TCF12 exon 16, with dependence on the silencing degree of MBNL1, In MBNL1 over-expressed HeLa cells we have found and validated by RT-qPCR a potent inclusion of CD44 exon 8, CD44 exon 11 and the 3´UTR of TRAF2. We have then mimicked the misregulation of MBNL1 and CELF1 protein levels of DM1 in HeLa cells, finding new altered splicing events. These alterations were found in genes that encode proteins involved in myoblast differentiation and migration (CD44, RASIP1) and muscle development (TCF12 transcription factor), estrogen and thyroid receptor interactor (LCOR), as well as proteins involved in transduction signaling pathways (PIP4K2C, TRAF2) and intracellular trafficking (KIF13A). These results provide potential contributing genes that could help to explain the complex phenotype of the DM1 disease.
2016-12-21 | GSE41987 | GEO
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein, we performed CLIP-seq against Celf1 using the 3B1 antibody, in myoblasts, heart tissue, and muscle tissue. RNA Bind-N-Seq was performed using recombinant CELF1 protein in the presence of competing amounts of recombinant MBNL1 protein.
2015-04-13 | E-GEOD-67337 | biostudies-arrayexpress
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart. Mice were engineered to express the reverse tetracycline trans-activator (rtTA) from a heart-specific alpha myosin heavy chain promoter, and an N-terminal Flag-tagged version of the LYLQ isoform of human Celf1 from a tet-inducible promoter. Mice were fed doxycycline to induce Celf1 expression in heart, and hearts were harvested from 3 mice each at 12 hour, 24 hour, 72 hour, and 7 day time points. To account for potential doxycycline-dependent effects, control mice were fed doxycycline for 72 hours but these mice did not contain the tet-inducible Celf1 cassette. In total, 15 hearts were analyzed by RNA-Seq.
2014-04-01 | E-GEOD-56185 | biostudies-arrayexpress
Project description:RNA-binding proteins (RBPs) are critical regulators of gene expression, but only a small fraction have been studied for their role in malignancy. Here we report a systematic analysis of RBP CUGBP Elav-Like Family member 1 (CELF1 alias CUGBP1) roles in mRNA alternative splicing, translation and turnover in oral cancer cells. CELF1 is overexpressed in carcinogen-induced oral cancer tumorigenesis mouse model and specific inhibition of CELF1 reduces tumor growth in vivo. Deep transcriptomic analysis revealed that hundreds of mRNAs were differentially regulated as a function of CELF1 expression in oral cancer cells. More importantly, the presence of CELF1 promoted alternative splicing of several target mRNAs which are known to be involved in various cancer biological processes. Using a pulse SILAC-based quantitative proteomic approach, we observed hundreds of proteins whose translation was controlled by CELF1 and those altered proteins were implicated in malignancy. Altogether, these data provided a comprehensive view of the CELF1 mRNA regulatory network in OSCC and suggests that CELF1 is a viable target for therapeutic intervention. Significance Post-transcriptional mechanisms that regulate cancer cells which are believed to constitute the driving force of many malignancies are poorly understood. We show that oral squamous cell carcinoma (OSCC) emerge as a result of an over expressed RNA-binding protein CELF1, a protein implicated in mRNA turnover, alternative splicing and translation. The resulting mRNA expression repertoire regulates networks of genes whose expression changes regulate oral cancer pathogenesis. Inhibition of CELF1 mitigated OSCC tumor-forming capacity and offers an attractive therapeutic option for oral malignancies. Transcriptomic analysis of UMSCC-74B oral cancer cells as a function of CELF1 protein expression.
2015-09-01 | E-GEOD-57254 | biostudies-arrayexpress
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart.
2014-04-01 | GSE56185 | GEO
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the muscle.
2014-12-01 | GSE61891 | GEO
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the muscle.
2014-12-01 | GSE61890 | GEO
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein, we performed CLIP-seq against Celf1 using the 3B1 antibody, in myoblasts, heart tissue, and muscle tissue.
2015-04-13 | GSE67337 | GEO
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein, we performed CLIP-seq against Celf1 using the 3B1 antibody, in myoblasts, heart tissue, and muscle tissue.
2014-12-01 | GSE61892 | GEO
Project description:The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated.
2016-10-22 | GSE85646 | GEO