Strand asymmetry in MPRA Signal
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ABSTRACT:
PROVIDER: PRJNA659269 | ENA |
REPOSITORIES: ENA
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Project description:We analyzed data from sequencing-based massively parallel reporter assays (MPRAs) retaining the strand orientation of the alignments. These analyses showed pervasive asymmetry in reporter signal from test element strand orientation. Present in elements derived from all regions of the human genome, we found test elements derived from gene bodies display concordant strand asymmetry with the sense orientation of the gene body. Furthermore, we observe that test elements form Alu sequence also present concordant strand asymmetry with Alu retrotransposon features. We establish sequence features that drive some of this asymmetry.
2020-12-04 | GSE156857 | GEO
Project description:Asymmetric selection of single-stranded guide RNAs from double-stranded RNA (dsRNA) precursors is crucial for RNA silencing-mediated gene regulation. However, the precise mechanisms for small RNA asymmetry remain unclear, especially since asymmetric selection can still occur under depletion of putative asymmetry sensors, Drosophila R2D2 and mammalian Dicer. Here we report direct contribution of mammalian Argonaute 2 (Ago2) to microRNA (miRNA) asymmetry. Ago2 selects strands with 5´-uridine/adenosine and thermodynamically unstable 5´-ends in parallel through its two sensor regions, which contact 5´-nucleobase and 5´-phosphate(s) of the prospective guide strands, respectively. Consistently, miRNA asymmetry shows characteristic digital-analog superposed patterns reflecting 5'-end nucleotide identity and thermodynamic stability. Furthermore, we demonstrate that cancer-associated miRNA variations reprogram asymmetric selection. Finally, our study presents a model of this universal principle that will aid a comprehensive understanding of miRNA function and therapeutic reinvention of RNA silencing in precision medicine.
2015-06-15 | GSE66022 | GEO
Project description:Homo sapiens and Macaca fascicularis neural progenitor cell lines were transduced with a lentiviral MPRA (Massively Parallel Reporter Assay) library. MPRA barcode sequencing and RNA-seq was performed on the extracted RNA. MPRA data was used to compare activity of regulatory sequences across 75 mammalian species with a focus on primates and correlate these activities with the Phenotype of gyrencephaly.
2021-05-12 | E-MTAB-9952 | biostudies-arrayexpress
Project description:Asymmetric selection of single-stranded guide RNAs from double-stranded RNA (dsRNA) precursors is crucial for RNA silencing-mediated gene regulation. However, the precise mechanisms for small RNA asymmetry remain unclear, especially since asymmetric selection can still occur under depletion of putative asymmetry sensors, Drosophila R2D2 and mammalian Dicer. Here we report direct contribution of mammalian Argonaute 2 (Ago2) to microRNA (miRNA) asymmetry. Ago2 selects strands with 5´-uridine/adenosine and thermodynamically unstable 5´-ends in parallel through its two sensor regions, which contact 5´-nucleobase and 5´-phosphate(s) of the prospective guide strands, respectively. Consistently, miRNA asymmetry shows characteristic digital-analog superposed patterns reflecting 5'-end nucleotide identity and thermodynamic stability. Furthermore, we demonstrate that cancer-associated miRNA variations reprogram asymmetric selection. Finally, our study presents a model of this universal principle that will aid a comprehensive understanding of miRNA function and therapeutic reinvention of RNA silencing in precision medicine. Immunoprecipitation of WT or mutant Ago2 in mouse ES cells (Ago-null background) and small RNA sequencing
2015-06-15 | E-GEOD-66022 | biostudies-arrayexpress
Project description:Whole genome expression analyses between wild-type Mycobacterium tuberculosis H37Rv and the isogenic mprA::Kmr mutant. Expression analyses between these strains were conducted following growth under physiological conditions, or following exposure to non-inhibitory concentrations of SDS or Triton X-100.
2006-03-01 | E-MEXP-552 | biostudies-arrayexpress
Project description:Non-syndromic facial asymmetry is commonly found in dentofacial deformity populations with skeletal malocclusions. Asymmetry of this type may result from imbalanced growth and function of both the jaw and associated muscles. Among the multiple genes that interact to affect the craniofacial musculoskeletal complex during pre and postnatal growth and development, NODAL signaling pathwy (NSP) genes are active in adult skeletal muscle and may be key factors in development, growth and maintenance of facial asymmetry. It is of interest to determine whether expression of NODAL pathway genes might differ in masseter muscles between individuals with malocclusion that have facial asymmetry and normal symmetry. Human Transcriptome 2.0 GeneChips (HTA2.0) were used to examine global gene expression in masster muscles between malocclusion subjects with posterior facial asymmetry and with normal facial symmetry. Eleven patients undergoing orthoganthic surgery were selected for comparison of masseter muscle gene expression on microarrays. Two subjects had posterior facial asymmetry (one with class II open bite and one with class III open bite malocclusion) and nine subjects had normal facial symmetry (three with class II open bite, two with class III open bite and four with class II deep bite malocclusion). RNA representative of total gene expression in masseter muscles of the malocclusion subjects with and without posterior facial asymmetry was prepared for labeling and hybridization on HTA2.0 chips. The two subjects with facial asymmetry clustered separately from eight other malocclusion subjects by a principle component analysis (PCA), even though one had a class II and the other a class III malocclusion. Sample 4L_Open_II is from a subject who has sleep apnea. Data from 4L_Open_II clustered independent of the asymmetry group and the eight other subjects of the symmetry group by PCA and was not included in analysis of differential expression with facial symmetry. Masseter muscles are paired jaw muscles (i.e. right and left masseter). In some cases, there was not sufficient quantity/quality of RNA from one side, thus the other side was used. Please note that the following information is provided in the 'source name' field of each sample record; subject ID number; either left or right masseter; J CRANIOFAC SURG_ID# corresponding to the data presented in the manuscript
2014-05-20 | E-GEOD-57775 | biostudies-arrayexpress
Project description:Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson's disease (PD), but its molecular determinants are unknown. Here, we determine epigenetic changes and genes involved in hemispheric asymmetry in the healthy and PD brain. Neurons of healthy individuals exhibit numerous hemispheric differences in DNA methylation, affecting genes implicated in neurodegenerative diseases. In PD patients, hemispheric asymmetry in DNA methylation is even greater and involves many PD risk genes. Moreover, the lateralization of clinical PD symptoms involves epigenetic, transcriptional, and proteomic differences across hemispheres that affect neurodevelopment, immune activation, and synaptic transmission. In aging, healthy neurons demonstrate a progressive loss of hemisphere asymmetry in epigenomes that is amplified in PD. For PD patients, a long disease course is associated with retaining more hemispheric asymmetry in neuronal epigenomes. Hemispheric differences in epigenetic gene regulation are prevalent in neurons and may affect the progression and symptoms of PD.
2020-03-26 | PXD015239 | Pride
Project description:Non-syndromic facial asymmetry is commonly found in dentofacial deformity populations with skeletal malocclusions. Asymmetry of this type may result from imbalanced growth and function of both the jaw and associated muscles. Among the multiple genes that interact to affect the craniofacial musculoskeletal complex during pre and postnatal growth and development, NODAL signaling pathwy (NSP) genes are active in adult skeletal muscle and may be key factors in development, growth and maintenance of facial asymmetry. It is of interest to determine whether expression of NODAL pathway genes might differ in masseter muscles between individuals with malocclusion that have facial asymmetry and normal symmetry. Human Transcriptome 2.0 GeneChips (HTA2.0) were used to examine global gene expression in masster muscles between malocclusion subjects with posterior facial asymmetry and with normal facial symmetry.
2014-05-20 | GSE57775 | GEO
Project description:Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide catalytic sequence-specific cleavage of fully or nearly fully complementary target mRNAs or control translation and/or stability of many mRNAs that share 6-8 nucleotides (nt) of complementarity to the siRNA and miRNA 5' end. siRNA- and miRNA-containing ribonucleoprotein silencing complexes are assembled from double-stranded 21- to 23-nt RNase III processing intermediates that carry 5' phosphates and 2-nt overhangs with free 3' hydroxyl groups. Despite the structural symmetry of a duplex siRNA, the nucleotide sequence asymmetry can generate a bias for preferred loading of one of the two duplex-forming strands into the RNA-induced silencing complex (RISC). Here we show that the 5'-phosphorylation status of the siRNA strands also acts as an important determinant for strand selection. 5'-O-methylated siRNA duplexes refractory to 5' phosphorylation were examined for their biases in siRNA strand selection. Asymmetric, single methylation of siRNA duplexes reduced the occupancy of the silencing complex by the methylated strand with concomitant elimination of its off-targeting signature and enhanced off-targeting signature of the phosphorylated strand. Methylation of both siRNA strands reduced but did not completely abolish RNA silencing, without affecting strand selection relative to that of the unmodified siRNA. We conclude that asymmetric 5' modification of siRNA duplexes can be useful for controlling targeting specificity. Keywords: siRNA, transfection, chemical modification, off-targets
2008-04-02 | GSE10960 | GEO
Project description:We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases. We used a functional approach (massively-parallel reporter assay; MPRA) to first identify active enhancers at the locus in primary human macrophages, and then determine if candidate variants within these regulatory regions might alter enhancer activity. In doing so, we discovered a mechanism that orchestrates macrophage responses during chronic inflammation and delineated how the risk haplotype increases expression of the causal gene, ETS2.
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