RNA transcription and degradation of Alu retrotransposons depends on sequence features and evolutionary history
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185485 | GEO | 2022/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in aM-BM- DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, includingM-BM- NanogM-BM- mRNA, which modulate exit from the proliferative stem-cell state. This regulation requiresM-BM- AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment ofM-BM- AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).
2012-12-29 | E-GEOD-42563 | biostudies-arrayexpress
Project description:Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program.
2012-12-29 | GSE42563 | GEO
Project description:More than 98% of the mammalian genome is noncoding and approximately half is made up of transposable elements. One of the most abundant is the short interspersed nuclear elements (SINE). Among the million copies of SINEs, B2 accounts for ~350,000 in the mouse genome and have garnered special interest because of emerging roles in gene regulation. Our recent work demonstrated that B2 RNA normally binds stress genes to retard transcription elongation. Though epigenetically silenced, B2s become massively upregulated during thermal stress. Specifically, an interaction between B2 RNA and the Polycomb protein, EZH2, results in cleavage of B2 RNA, release of B2 RNA from RNA Polymerase II, and activation of the stress genes. Although an established RNA-binding protein and histone methyltransferase, EZH2 is not known to be a nuclease. Here, we provide evidence for the surprising conclusion that B2 is a self-cleaving RNA. Contact with EZH2 accelerates cleavage rate by >100-fold, suggesting that EZH2 may assist cleavage as an RNA chaperone. Modification-interference analysis demonstrate that phosphorothioate changes at A and C nucleotides can substitute for EZH2’s function. B2 mutagenesis indicate that nucleotides around positions 45-55 and 100-101 are critical for cleavage reaction. Finally, we demonstrate that another family of SINEs, the ALU elements produce also a self-cleaving RNA. ALUs are intrinsically more auto-reactive than B2s. We propose that the B2/ALU SINEs are a new class of ribozymes whose activity is accelerated by EZH2.
2020-01-31 | GSE139931 | GEO
Project description:LINE-1 and Alu retrotransposons are components of the human genome and have been implicated in many human diseases. These elements can influence human transcriptome plasticity in various mechanisms. Chimeric transcripts derived from LINE-1 and Alu can also impact the human transcriptome, such as exonization and post-transcriptional modification. However, its specific role in ASD neuropathology remains unclear, particularly in the cerebellum tissues. We performed RNA-sequencing of post-mortem cerebellum tissues from ASD and unaffected individuals for transposable elements profiling and chimeric transcript identification. The majority of free transcripts of transposable elements were not changed in the cerebellum tissues of ASD compared with unaffected individuals. Nevertheless, we observed that chimeric transcripts derived from LINE-1 and Alu were embedded in the transcripts of differentially expressed genes in the cerebellum of ASD, and these genes were related to developments and abnormalities of the cerebellum. In addition, the expression levels of these genes were correlated with the significantly decreased thickness of the molecular layer in the cerebellum of ASD. We also found that global methylation and expression of LINE-1 and Alu elements were not changed in ASD, but observed in the ASD sub-phenotypes. Our findings showed associations between transposable elements and cerebellar abnormalities in ASD, particularly in distinct phenotypic subgroups. Further investigations using appropriate models are warranted to elucidate the structural and functional implications of LINE-1 and Alu elements in ASD neuropathology.
2024-08-22 | GSE269105 | GEO
Project description:While liganded nuclear receptors are well established to regulate Pol II protein-coding transcription units, their role in regulation of DNA repeats remains largely unknown. Here, we report that ~2-3% of the ~1-200,000 human DR2 Alu repeats, particularly those in proximity to retinoic acid-activated Pol II transcription units, are bound and activated by retinoic acid receptor in human embryonic stem cells, triggering their Pol III-dependent transcription. The non-coding DR2 Alu transcripts are processed in a Dicer-dependent fashion into a series of small RNA products with sizes ranging ~28-65nt and exhibit substantial co-localization with P bodies. These small RNAs cause degradation of a subset of mRNAs critical for the "stem cell" state, which harbor complimentary sequences in their 3' untranslated regions. This regulation requires Ago3- dependent stabilization of full-length and processed DR2 Alu transcripts, and recruitment of Ago3-associated decapping complexes to the target mRNAs. Thus, the RAR/Pol III-dependent DR2 Alu transcriptional program in stem cells serves as a functional complement to the RAR/Pol II-dependent counterpart. ChIP-seq of H3K36me3 samples before and after RA (retinoic acid) treatments.
2012-09-01 | E-GEOD-30876 | biostudies-arrayexpress
Project description:While liganded nuclear receptors are well established to regulate Pol II protein-coding transcription units, their role in regulation of DNA repeats remains largely unknown. Here, we report that ~2-3% of the ~1-200,000 human DR2 Alu repeats, particularly those in proximity to retinoic acid-activated Pol II transcription units, are bound and activated by retinoic acid receptor in human embryonic stem cells, triggering their Pol III-dependent transcription. The non-coding DR2 Alu transcripts are processed in a Dicer-dependent fashion into a series of small RNA products with sizes ranging ~28-65nt and exhibit substantial co-localization with P bodies. These small RNAs cause degradation of a subset of mRNAs critical for the "stem cell" state, which harbor complimentary sequences in their 3' untranslated regions. This regulation requires Ago3- dependent stabilization of full-length and processed DR2 Alu transcripts, and recruitment of Ago3-associated decapping complexes to the target mRNAs. Thus, the RAR/Pol III-dependent DR2 Alu transcriptional program in stem cells serves as a functional complement to the RAR/Pol II-dependent counterpart.
2012-09-01 | GSE30876 | GEO
Project description:Alu SINEs are the most numerous frequently occurring transcription units in our genomes and possess sequence competence for transcription by RNA Pol III. However, through poorly understood mechanisms, the Alu RNA levels are maintained at very low levels in normal somatic cells with obvious benefits of low rates of Alu retrotransposition and energy-economical deployment of RNA Pol III to the tRNA genes which share promoter structure and polymerase requirements with Alu SINEs. Using comparative ChIP sequencing, we unveil that a repeat binding protein, CGGBP1, binds to the transcriptional regulatory regions of Alu SINEs thereby impeding Alu transcription by inhibiting RNA Pol III recruitment. We show that this Alu-silencing depends on growth factor stimulation of cells and subsequent tyrosine phosphorylation of CGGBP1. Importantly, CGGBP1 ensures a sequence-specific discriminative inhibition of RNA Pol III activity at Alu promoters, while sparing the structurally similar tRNA promoters. Our data suggest that CGGBP1 contributes to growth-related transcription by preventing the hijacking of RNA Pol III by Alu SINEs. Examination of one DNA binding protein in two different conditions of treatment.
2015-04-29 | E-GEOD-53571 | biostudies-arrayexpress
Project description:Alu SINEs are the most numerous frequently occurring transcription units in our genomes and possess sequence competence for transcription by RNA Pol III. However, through poorly understood mechanisms, the Alu RNA levels are maintained at very low levels in normal somatic cells with obvious benefits of low rates of Alu retrotransposition and energy-economical deployment of RNA Pol III to the tRNA genes which share promoter structure and polymerase requirements with Alu SINEs. Using comparative ChIP sequencing, we unveil that a repeat binding protein, CGGBP1, binds to the transcriptional regulatory regions of Alu SINEs thereby impeding Alu transcription by inhibiting RNA Pol III recruitment. We show that this Alu-silencing depends on growth factor stimulation of cells and subsequent tyrosine phosphorylation of CGGBP1. Importantly, CGGBP1 ensures a sequence-specific discriminative inhibition of RNA Pol III activity at Alu promoters, while sparing the structurally similar tRNA promoters. Our data suggest that CGGBP1 contributes to growth-related transcription by preventing the hijacking of RNA Pol III by Alu SINEs.
2015-04-29 | GSE53571 | GEO
Project description:Alu SINEs are the most numerous frequently occurring transcription units in our genome and possess sequence competence for transcription by RNA Pol III. However, through poorly understood mechanisms, the Alu RNA levels are maintained at very low levels in normal somatic cells with obvious benefits of low rates of Alu retrotransposition and energy-economical deployment of RNA Pol III to the tRNA genes which share promoter structure and polymerase requirements with Alu SINEs. Using comparative ChIP sequencing, we unveil that a repeat binding protein, CGGBP1, binds to the transcriptional regulatory regions of Alu SINEs thereby impeding Alu transcription by inhibiting RNA Pol III recruitment. We show that this Alu-silencing depends on growth factor stimulation of cells and subsequent tyrosine phosphorylation of CGGBP1. Importantly, CGGBP1 ensures a sequence-specific discriminative inhibition of RNA Pol III activity at Alu promoters, while sparing the structurally similar tRNA promoters. Our data suggest that CGGBP1 contributes to growth-related transcription by preventing the hijacking of RNA Pol III by Alu SINEs. This study was used to find out the effect of CGGBP1 on serum-induced changes in gene expression and effect of serum on gene expression regulation by CGGBP1. Gene expression profiling of normal human fibroblasts under 4 different experimental perturbations: serum starvation or serum stimulation and CGGBP1 depletion or normal CGGBP1 levels.
2015-12-21 | E-GEOD-54058 | biostudies-arrayexpress
Project description:Alu SINEs are the most numerous frequently occurring transcription units in our genome and possess sequence competence for transcription by RNA Pol III. However, through poorly understood mechanisms, the Alu RNA levels are maintained at very low levels in normal somatic cells with obvious benefits of low rates of Alu retrotransposition and energy-economical deployment of RNA Pol III to the tRNA genes which share promoter structure and polymerase requirements with Alu SINEs. Using comparative ChIP sequencing, we unveil that a repeat binding protein, CGGBP1, binds to the transcriptional regulatory regions of Alu SINEs thereby impeding Alu transcription by inhibiting RNA Pol III recruitment. We show that this Alu-silencing depends on growth factor stimulation of cells and subsequent tyrosine phosphorylation of CGGBP1. Importantly, CGGBP1 ensures a sequence-specific discriminative inhibition of RNA Pol III activity at Alu promoters, while sparing the structurally similar tRNA promoters. Our data suggest that CGGBP1 contributes to growth-related transcription by preventing the hijacking of RNA Pol III by Alu SINEs. This study was used to find out the effect of CGGBP1 on serum-induced changes in gene expression and effect of serum on gene expression regulation by CGGBP1.
2015-12-21 | GSE54058 | GEO