Transcriptomic analysis of HeLa cells depleted in CELF1, ELAVL1, and both
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PROVIDER: PRJNA487606 | ENA |
REPOSITORIES: ENA
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Project description:ELAVL1 and CELF1 are two RNA-binding proteins involved in alternative splicing control. To address their functional relationships, we identify the differentially spliced mRNAs upon depletion of CELF1, ELAVL1, or both. These proteins control similar sets of genes with similar consequences on exon inclusion or skipping. The magnitude of the effect of the double depletion equals the sum of the magnitudes of the individual depletions, showing that CELF1 and ELAVL1 additively control their target RNAs. CELF1 and ELAVL1 regulated splicing events include ACSL4, WNK1, CD44, MICAL3, and JDP2. Using FRET, we find that CELF1 and ELAVL1 directly interact in cell nuclei. We demonstrate that the combined levels of CELF1 and ELAVL1 is a valuable biomarker in breast cancer, while their levels bring very limited information when taken individually. A “co-RNA splicing map” of CELF1 and ELAVL1 shows they repress alternative splice sites when bound nearby, but activate them when bound further away. Together, these data point to strong functional interactions between CELF1 and ELAVL1 to control alternative splicing with significant impacts in human pathology.
2021-08-01 | GSE118981 | GEO
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:Purpose: The goal of this study is to compare the transcriptome changes between Negative control, UBR5 depleted and MYC depleted HeLa cells Methods: Gene expression profiles of Negative control, UBR5 depleted and MYC depleted HeLa cells were generated by deep sequencing, in triplicate. Results:The data were analyzed, and we sucessfully detected global differences in the gene expression between the given groups. Conclusions: UBR5 depletion induces gene expression changes that are partly overlapping with gene expression changes induced by MYC depletion
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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.
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Project description:We generated a HeLa cell model of mucopolysaccharidosis IIIB (MPSIIIB) by depleting NAGLU. MPSIIIB-associated cell defects were prominent in NAGLU-depleted cells. We explored alterations of metabolic pathways in NAGLU-depleted cells versus non-depleted control cells by performing gene expression profiling. Exon array transcriptome analysis showed 96 transcripts with increased expression level and 38 transcripts with decreased expression level in NAGLU-depleted versus non-depleted cells.
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Project description:As a multifunctional RBP, CELF1 is known to preferentially binds to GU-rich elements (GREs) predominantly located in 3’ untranslated regions(UTRs) of target mRNA to regulate various post-transcriptional process. However, the targeted genes that regulated by CELF1 during cataractogenesis remains unknown. In present study,the function of CELF1 in SRA01/04 cells was investigated with CELF1 overexpression, the expression of MMPs was regulated by CELF1.
2022-03-23 | GSE153022 | GEO
Project description:Celf1 germline or conditional deletion mouse mutants exhibit fully penetrant lens defects including cataract. To gain insight into gene expression changes underlying these lens defects, microarray comparison was performed for lenses obtained from control and Celf1 conditional deletion mutant mice.
2023-02-18 | GSE225303 | 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 heart.
2014-04-01 | GSE56185 | GEO
Project description:We generated a HeLa cell model of mucopolysaccharidosis IIIB (MPSIIIB) by depleting NAGLU. MPSIIIB-associated cell defects were prominent in NAGLU-depleted cells. We explored alterations of metabolic pathways in NAGLU-depleted cells versus non-depleted control cells by performing gene expression profiling. Exon array transcriptome analysis showed 96 transcripts with increased expression level and 38 transcripts with decreased expression level in NAGLU-depleted versus non-depleted cells. Total RNA was extracted from two independent cultures of non-depleted cells and NAGLU-depleted cells. We considered a minimal fold change of 1.5 fold and a corrected P value lower than 0.05.
2012-09-13 | E-GEOD-32154 | biostudies-arrayexpress
Project description:To understand the polyadenylation site usage at the transcriptome level before and after CFIm25 depletion, we carried out 3'-seq analysis in control and CFIm25-depleted HeLa cells using 3'-seq kit (Lexogen, 016.24)
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