Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA127851 | ENA |
REPOSITORIES: ENA
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Project description:Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell type-specific AS in a concentration and phosphorylation dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 changes AS of endogenous pre-mRNAs, similar to what was observed upon overexpression of SR proteins. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight a novel role for a nrRNA in the regulation of gene expression. Malat1 Antisense and control knockdowns evaluated on a microarray platform to profile alternative splicing levels for 5782 cassette-type alternative exons.
2010-09-01 | E-GEOD-22963 | biostudies-arrayexpress
Project description:Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell type-specific AS in a concentration and phosphorylation dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 changes AS of endogenous pre-mRNAs, similar to what was observed upon overexpression of SR proteins. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight a novel role for a nrRNA in the regulation of gene expression.
2010-09-01 | GSE22963 | GEO
Project description:The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or premRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation. Keywords: MALAT1; MALAT-1, NEAT2, ncRNA; E2F, alternative splicing; pre-mRNA splicing factors WI38 cells (normal human diploid fibroblasts) were transfected with a control oligo (CTR) or antisense oligos to MALAT1 and RNA was isolated after 48 hr. Two antisense oligos were use for MALAT1 (AS-1 and AS-2). Arrays were done for 3 sets of samples in triplicate (control, AS-1 and AS-2).
2014-05-16 | E-GEOD-44240 | biostudies-arrayexpress
Project description:Hypoxia-induced alternative splicing (AS) controls tumor progression and metastasis. The underlying mechanism specifying hypoxia-responsive AS needs to be determined. We demonstrate the role of nuclear speckle (speckle) nuclear domain (ND) and the long noncoding RNA, MALAT1, in hypoxia-responsive AS. Hypoxia-responsive genes position near speckles, the NDs that enhance splicing efficiency, and their differentially spliced exons harbor features that are characteristic of inefficiently spliced transcripts. Speckle-resident MALAT1, induced in response to hypoxia, boosts hypoxia-responsive AS by regulating the binding of SR-family splicing factor1 (SRSF1) to pre-mRNAs of speckle-associated genes. Mechanistically, MALAT1 facilitates the recruitment of SRSF1 to elongating RNA pol II (RNAP II) by promoting the formation of phase-separated SRSF1 condensates that are preferentially recognized and recruited to pre-mRNA by RNAP II. Our results reveal that MALAT1 boosts hypoxia-induced AS of speckle-associated genes by establishing the threshold concentration of SRSF1 as condensates, thereby promoting RNAP II-mediated recruitment of SRSF1 to pre-mRNAs.
2026-03-27 | GSE285088 | GEO
Project description:Hypoxia-induced alternative splicing (AS) controls tumor progression and metastasis. The underlying mechanism specifying hypoxia-responsive AS needs to be determined. We demonstrate the role of nuclear speckle (speckle) nuclear domain (ND) and the long noncoding RNA, MALAT1, in hypoxia-responsive AS. Hypoxia-responsive genes position near speckles, the NDs that enhance splicing efficiency, and their differentially spliced exons harbor features that are characteristic of inefficiently spliced transcripts. Speckle-resident MALAT1, induced in response to hypoxia, boosts hypoxia-responsive AS by regulating the binding of SR-family splicing factor1 (SRSF1) to pre-mRNAs of speckle-associated genes. Mechanistically, MALAT1 facilitates the recruitment of SRSF1 to elongating RNA pol II (RNAP II) by promoting the formation of phase-separated SRSF1 condensates that are preferentially recognized and recruited to pre-mRNA by RNAP II. Our results reveal that MALAT1 boosts hypoxia-induced AS of speckle-associated genes by establishing the threshold concentration of SRSF1 as condensates, thereby promoting RNAP II-mediated recruitment of SRSF1 to pre-mRNAs.
2026-03-27 | GSE285077 | GEO
Project description:Hypoxia-induced alternative splicing (AS) controls tumor progression and metastasis. The underlying mechanism specifying hypoxia-responsive AS needs to be determined. We demonstrate the role of nuclear speckle (speckle) nuclear domain (ND) and the long noncoding RNA, MALAT1, in hypoxia-responsive AS. Hypoxia-responsive genes position near speckles, the NDs that enhance splicing efficiency, and their differentially spliced exons harbor features that are characteristic of inefficiently spliced transcripts. Speckle-resident MALAT1, induced in response to hypoxia, boosts hypoxia-responsive AS by regulating the binding of SR-family splicing factor1 (SRSF1) to pre-mRNAs of speckle-associated genes. Mechanistically, MALAT1 facilitates the recruitment of SRSF1 to elongating RNA pol II (RNAP II) by promoting the formation of phase-separated SRSF1 condensates that are preferentially recognized and recruited to pre-mRNA by RNAP II. Our results reveal that MALAT1 boosts hypoxia-induced AS of speckle-associated genes by establishing the threshold concentration of SRSF1 as condensates, thereby promoting RNAP II-mediated recruitment of SRSF1 to pre-mRNAs.
2026-03-27 | GSE285089 | GEO
Project description:Hypoxia-induced alternative splicing (AS) controls tumor progression and metastasis. The underlying mechanism specifying hypoxia-responsive AS needs to be determined. We demonstrate the role of nuclear speckle (speckle) nuclear domain (ND) and the long noncoding RNA, MALAT1, in hypoxia-responsive AS. Hypoxia-responsive genes position near speckles, the NDs that enhance splicing efficiency, and their differentially spliced exons harbor features that are characteristic of inefficiently spliced transcripts. Speckle-resident MALAT1, induced in response to hypoxia, boosts hypoxia-responsive AS by regulating the binding of SR-family splicing factor1 (SRSF1) to pre-mRNAs of speckle-associated genes. Mechanistically, MALAT1 facilitates the recruitment of SRSF1 to elongating RNA pol II (RNAP II) by promoting the formation of phase-separated SRSF1 condensates that are preferentially recognized and recruited to pre-mRNA by RNAP II. Our results reveal that MALAT1 boosts hypoxia-induced AS of speckle-associated genes by establishing the threshold concentration of SRSF1 as condensates, thereby promoting RNAP II-mediated recruitment of SRSF1 to pre-mRNAs.
2026-03-27 | GSE311108 | GEO
Project description:Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1. To address if the the absence of Malat1 affects the expression of other genes, including other long noncoding RNA, microarrays were used to study the impact of knocking-out Malat1 on global gene expression in mouse embryonic fibroblasts (MEFs). MEFs were prepared from E13.5 mouse embryos from wildtype and Malat1 knock-out mice. RNA harvested from these cells were hybridized to Affymetirx mouse gene expression array.
2012-06-24 | E-GEOD-37705 | biostudies-arrayexpress
Project description:Transcriptome analysis of control and MALAT1 lncRNA-depleted RNA samples from human diploid lung fibroblasts [WI38] The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or pre-mRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation. We analyzed RNA from control and MALAT1 depleted WI38 cells using the Affymetrix Human Exon 1.0 ST platform. Array data was analyzed by Partek Genomic Suite software.
2013-01-29 | E-GEOD-43830 | biostudies-arrayexpress
Project description:The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or premRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation. Keywords: MALAT1; MALAT-1, NEAT2, ncRNA; E2F, alternative splicing; pre-mRNA splicing factors
2014-05-16 | GSE44240 | GEO