Similar Datasets
Project description:Splicing regulation by the lncRNA ASCO
| PRJNA558687 | ENA
Project description:Mammalian genomes are pervasively transcribed to produce thousands of spliced long noncoding RNAs (lncRNAs), whose functions remain poorly understood. Because recent evidence has implicated several specific lncRNA loci in the local regulation of gene expression, we sought to determine whether such local regulation is a property of many lncRNA loci. We used genetic manipulations to dissect 12 genomic loci that produce lncRNAs and found that 5 of these loci influence the expression of a neighboring gene in cis. Surprisingly, however, none of these effects required the specific lncRNA transcripts themselves and instead involved general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Interestingly, such effects are not limited to lncRNA loci: we found similar effects on local gene expression at 4 of 6 protein-coding loci. These results demonstrate that ‘crosstalk’ among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms and cis regulatory signals, including a novel role for RNA splice sites. These mechanisms may coordinate the expression of neighboring genes and explain the function and evolution of some genomic loci that produce lncRNAs.
2016-10-28 | GSE85798 | GEO
Project description:Herpesvirus-encoded lncRNA targets host splicing by sequestering splicing factors
| PRJNA1368624 | ENA
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple short and long noncoding RNAs which contribute to viral latency, persistence, host gene regulation, and immune evasion. The Antisense-to-Latency Transcript (ALT) is a ~10 kb long noncoding RNA (lncRNA) located on the opposite strand of the major latency-associated region encoding the latency associated nuclear antigen, vCyclin, vFLIP, the Kaposin's and 12 microRNA genes. ALT is a nuclear lncRNA that is lowly expressed during latency, but strongly upregulated during lytic replication. Using RNA antisense purification and quantitative mass spectrometry (RAP-MS) in lytically induced primary effusion lymphoma cells, we identified 51 human and 3 viral proteins that directly interact with ALT. Of these enriched proteins, 48 are splicing factors, including core and alternative splicing proteins, such as U2AF2, PTBP1/2, SRSF1/3 and MBNL1. Interaction and co-localization of ALT was confirmed with various splicing factors in ribonucleoprotein complexes suggesting that ALT sequesters splicing factors in nuclear condensates. We further identified that induction of lytic replication in lymphoid and epithelial cells leads to thousands of host gene splicing changes, which are partially restored upon perturbation of ALT expression. Finally, transient knockdown of ALT strongly inhibits viral reactivation and virion production. Hence, sequestering of splicing factors by ALT, interferes with host gene expression. Our results uncover a novel mechanism that shifts gene expression from the host to the virus late during the viral replication cycle to efficiently produce progeny virus and potentially antagonize host immune defenses.
2026-02-18 | GSE311068 | GEO
Project description:While long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional
2016-11-09 | GSE80045 | GEO
Project description:While long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional
2016-11-09 | GSE80043 | GEO
Project description:Differential lncRNA expression upon hypoxia affects splicing efficiency
| PRJNA530983 | ENA
Project description:MALAT1, an abundant lncRNA specifically localized to nuclear speckles, regulates alternative-splicing (AS). The molecular basis of its role in AS remains poorly understood. Here, we report three conserved, thermodynamically stable, parallel RNA-G-quadruplexes (rG4s) present in the 3’ region of MALAT1 which regulates this function. Using rG4 domain specific RNA-pull-down followed by mass-spectrometry, RNA-immuno-precipitation and imaging, we demonstrate the rG4 dependent localization of Nucleolin (NCL) and Nucleophosmin (NPM) to nuclear speckles. Specific G-to-A mutations that abolish rG4 structures, results in the localization loss of both the proteins from speckles. Functionally, disruption of rG4 in MALAT1 phenocopies NCL knockdown resulting in altered pre-mRNA splicing of endogenous genes. These results reveal a central role of rG4s within the 3’ region of MALAT1 orchestrating AS.
2022-02-17 | PXD026386 | Pride
Project description:Serine/arginine-rich splicing factor 3 (SRSF3) functions to regulate mRNA alternative splicing, a molecular mechanism to process more than 90% of the protein-coding genes and provides an essential source for the biological versatility and targeting of SRSF3 could be a novel approach for cancer therapy. This study identify that SRSF3 expression was upregulated in pancreatic cancer tissues and associated with drug resistance and poor prognosis. Thus, we found that SRSF3 regulated ANRIL splicing and modified m6A modification of ANRIL in pancreatic cancer cells. More importantly, we demonstrated that the m6A methylation on lncRNA-ANRIL was essential for splicing process. Meanwhile, we also found that the different isoforms of ANRIL were differentially expressed in drug-resistant pancreatic cancer cell lines, and SRSF3 promotes gemcitabine resistance by regulating the expression of ANRIL-208. In addition, ANRIL-208 regulated pancreatic cancer cell chemoresistance by forming a complex with Ring1b and EZH2 and enhanced DNA homologous recombination repair (HR) capacity. In conclusion, the current study first established the link among SRSF3, m6A modification, lncRNA splicing, and DNA HR repair in pancreatic cancer, and first demonstrated that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.
2022-05-11 | GSE197352 | GEO
Project description:Serine/arginine-rich splicing factor 3 (SRSF3) functions to regulate mRNA alternative splicing, a molecular mechanism to process more than 90% of the protein-coding genes and provides an essential source for the biological versatility and targeting of SRSF3 could be a novel approach for cancer therapy. This study identify that SRSF3 expression was upregulated in pancreatic cancer tissues and associated with drug resistance and poor prognosis. Thus, we found that SRSF3 regulated ANRIL splicing and modified m6A modification of ANRIL in pancreatic cancer cells. More importantly, we demonstrated that the m6A methylation on lncRNA-ANRIL was essential for splicing process. Meanwhile, we also found that the different isoforms of ANRIL were differentially expressed in drug-resistant pancreatic cancer cell lines, and SRSF3 promotes gemcitabine resistance by regulating the expression of ANRIL-208. In addition, ANRIL-208 regulated pancreatic cancer cell chemoresistance by forming a complex with Ring1b and EZH2 and enhanced DNA homologous recombination repair (HR) capacity. In conclusion, the current study first established the link among SRSF3, m6A modification, lncRNA splicing, and DNA HR repair in pancreatic cancer, and first demonstrated that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.
2022-05-11 | GSE197532 | GEO