SINE transposons
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ABSTRACT:
PROVIDER: PRJNA665855 | ENA |
REPOSITORIES: ENA
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Project description:Short interspersed element (SINE) RNAs are upregulated by cellular stresses1 (heat shock, DNA damage and viral infection) and accumulate in human diseases (macular degeneration2, lupus3, and Alzheimer’s disease4). These transcripts activate inflammasomes5, a family of cytoplasmic multiprotein complexes that sense danger molecules and initiate innate immune responses by activating caspase-1-dependent cytokine production and inflammatory death6, but the molecular sensor of SINE RNAs is unknown. Here, we identify DDX17, a member of the DEAD box family of RNA helicases7, as a sensor of SINE RNAs requisite for inflammasome activation. Induction of caspase-1 cleavage and release of IL-1 and IL-18 by SINE RNAs requires dual recruitment of NLRP3 and NLRC4 but proceeds independent of NAIPs, immune sensors required for canonical NLRC4 activation by bacterial proteins8,9. Instead, SINE RNAs trigger DDX17–NLRC4 interaction, which licenses inflammasome activation. We also report increased levels of DDX17 protein and association of DDX17 and NLRC4 in the retinal pigmented epithelium (RPE) of human eyes with an advanced, untreatable form of age-related macular degeneration (AMD). Disrupting DDX17–NLRC4 signalling blocks SINE RNA-induced inflammasome activation in human RPE cells and RPE degeneration in an animal model of AMD. Our findings uncover a non-canonical mode of inflammasome activation by endogenous retrotransposon transcripts, and provide new potential targets for macular degeneration and potentially other diseases.
2022-06-09 | PXD016019 | Pride
Project description:Morus alba L. Raw protein sequence reads and sequence
2024-02-08 | PXD049451 | iProX
Project description:Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28,270 SINE loci, with ~50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.
2016-10-31 | GSE85518 | GEO
Project description:We identified a novel long non-coding RNA Lx8-SINE B2, that is a marker of pluripotency. Depletion of Lx8-SINE B2 impacts embryonic stem cell self-renewal. RNA-seq analysis of Lx8-SINE B2 depletion revealed that a number of glycolytic genes with decreased expression. Mechanistically, we found that the Lx8-SINE B2 activates the glycolysis pathway by binding to Eno1. Collectively, our data suggest that Lx8-SINE B2 maintains the self-renewal of mESCs through glycolysis.
2022-09-19 | GSE182247 | GEO
Project description:We report genome-wide binding of the highly conserved TF Sine oculis (So), which is necessary for Drosophila eye development and has few previously known direct transcriptional targets. Our data identify novel putative targets of So-mediated regulation, including genes involved in multiple aspects of development. 2 biological replicates of ChIP-seq with anti-So antibody on chromatin from D. melanogaster third instar eye-antennal imaginal discs; negative control - same sample and ChIP-seq protocol without anti-So antibody
2014-03-17 | E-GEOD-52943 | biostudies-arrayexpress
Project description:SINEUPs are long non-coding RNAs which contain a functionally crucial SINE repeat element and positively regulate target mRNA translation at post-transcription level. To study secondary (2D) structure of these functional SINE-derived RNAs, various SINEUP-GFP plasmids containing different mouse SINEB2 repeat elements or human SINE FRAM repeat were transfected along with sense EGFP plasmid in HEK293T/17 cells. Total RNA in transfected cells were probed at flexible regions with NAI-N3 reagent and icSHAPE (in-vivo click selective hydroxyl acylation and profiling experiment) libraries were prepared. To further understand the structure dynamics of SINE transcripts in subcellular locations, cells were fractionated in nuclear and cytoplasmic fractions after 24 h of transfection and fraction-specific icSHAPE libraries were constructed.
2023-02-06 | GSE224534 | GEO
Project description:To identify the eye-enriched genes by comparing the mRNA expression profiles from wild type fly heads (CantonS) and eye-less fly heads (sine occulis).
2012-05-17 | E-MEXP-49 | biostudies-arrayexpress
Project description:We report genome-wide binding of the highly conserved TF Sine oculis (So), which is necessary for Drosophila eye development and has few previously known direct transcriptional targets. Our data identify novel putative targets of So-mediated regulation, including genes involved in multiple aspects of development.
2014-03-17 | GSE52943 | GEO
Project description:To determine the mechanism of SINE resistance, we compared RNA expression between parental and SINE resistant ovarian cancer cells.
2019-02-14 | GSE126519 | GEO