Post-transcriptional regulation by Alu within mRNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kung-Hao Liang
PROVIDER: E-GEOD-39822 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:An extrachromosomal replication system was established to examine the perturbation of Alu-carrying genes in response to elevated Alu RNAs in the opposite direction. The null hypothesis is that the Alu-carrying RNA duplex cannot trigger subsequent post-transcriptional regulation, manifesting a random perturbation of expression levels.
2013-05-13 | GSE39822 | GEO
Project description:Alu element is a major contributor to lineage-specific new exons in the primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements (such as Alu) are restricted to regulatory functions but do not have adequate evolutionary time to be incorporated into stable, functional proteins. In this work, we adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and mass spectrometry data of diverse human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances even between humans and closely related nonhuman primates. In the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA editing analyses of RNA-sequencing data demonstrate that both the Alu exon skipping and inclusion isoforms encode active RNA editing enzymes, while the Alu exon peptide may fine tune the editing activities of the ADARB1 protein products . Together, our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution. Comparing the A-I RNA editing levels during HEK293 (control), ADARB1 long isoform (with Alu exon) transfected, and short isoform (without Alu exon) transfected cells, each group has 3 replicates.
2015-12-10 | E-GEOD-65999 | biostudies-arrayexpress
Project description:Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression regulators, might be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblast and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-Sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry, including increased expression of the key cell cycle transcriptional regulator FOXM1 and several FOXM1-regulated genes. Overall, the results of our analysis suggest that increased Alu RNA favors cell cycle progression thus contributing to enable sustained cell proliferation which is an important factor of cancer development and progression.
2019-06-21 | GSE133078 | 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:Weaker CEBPA binding in the human than in the mouse genome is a general trait of the human genome across multiple biological conditions. Alu repeats carry strong CEBPA binding motifs, which compete with regulatory regions for CEBPA binding. To directly test this hypothesis, we attempted to overcome Alu competition by using, first, a CRISPR-dCas9 system in BLaER1 cells (Rapino et al. 2013). By promoting the recruitment of the inactive Cas9 to Alu regions with specific gRNAs targeting Alu repeats containing strong CEBPA motifs we protected them, hampering CEBPA binding to these regions. We tested the effect of two different paired gRNA constructs in two replicates and one control paired gRNA in two replicates. Second, we also further overexpressed CEBPA in human BLaER1 cells to overcome Alu competition. We tested two doses of CEBPA overexpression in two replicates and one control experiment in two replicates.
2023-05-01 | E-MTAB-12597 | biostudies-arrayexpress
Project description:Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the role of Alu has not been studied comprehensively in brain tumor because an evolutionary perspective has been the subject of little research in brain tumor. We aim to investigate the relevance of Alu to the gliomagenesis.
2021-01-27 | GSE165595 | GEO
Project description:Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RIC-seq technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs in HeLa cells. Here, we apply this technology to generate high-confidence enhancer-promoter RNA interaction (EPRI) maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Importantly, mapping 535,404 noncoding risk variants back to the EPRI maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.
2023-05-11 | GSE190214 | GEO
Project description:Next Generation Sequencing of Unmethylated Alu (NSUMA) interrogation of more than 130,000 individual Alus for differential methylation with concomitant analysis of copy number variations applied to the study of hypomethylation in primates. 3 replicates of Gorilla gorilla, Pan troglodytes, Pongo pygmaeus and Homo sapiens were studied.
2015-09-10 | E-GEOD-72877 | biostudies-arrayexpress
Project description:To identify the genome-wide impact of Alu/Alu-mediated rearrangement (AAMR) on variation and human health, we have developed a bioinformatic approach to characterize Alus involved in mediating CNVs and have predicted genome-wide AAMR hotspot loci. This prediction was validated by performing molecular biological experiments on 89 samples selected by correlating AAMR hotspot genes with a database of ~54,000 chromosomal microarrays.
2017-06-29 | GSE100590 | GEO
Project description:Alu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products. Our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution.
2015-12-10 | GSE65999 | GEO