Project description:Abnormal DNA sensing mediated by cGAS-STING is pivotal for host defenses. Activation of cGAS-STING triggered interferon dependent anti-viral functions have been well characterized but this function is missing in more ancient animal STING. Whether more primitive animal STING can generate non-canonical pathway dependent anti-viral activities is unclear. Here, we discovered potent anti-viral activities of ancient animal STING in the absence of all three canonical pathways. Various ancient animal STING-stimulated genes (ASGs) with unique and synergistic anti-viral functions were induced by this newly identified pathway through an ancient transcriptional regulator IRF1 and a separate unique functional domain in STING. Some ASGs are both necessary and sufficient as host restriction factors and under positive selection during animal evolution. Diverse viruses have developed strategies to evade this newly identified cGAS-STING function. Our findings reveal an ancient, conserved cGAS-STING pathway mediated anti-viral activities through previously unrecognized cellular restriction factors. Various animal STING expression in HEK293T cells could up regulate a series of genes. To screen candidates for anti-viral host factors stimulated by STING in the absence of the known canonical pathways, we identified the factors that were regulated by the IFN induction and NF-κB induction-defective Nematostella vectensis (N.v) STING and the IFN induction-defective human STING variant (H.s STING ΔCTT) by microarray assay. Multiple rounds of confirmative and comparative experiments narrowed down to 10 such factors, i.e., ancient animal STING stimulated genes (ASGs). ASGs were significantly upregulated by STING activation in various human cell types.
2025-03-28 | GSE293086 | GEO
Project description:Seeking the identity of an enigmatic moss by embracing phylogenomics
Project description:Circular RNAs (circRNAs) in animals are an enigmatic class of RNAs with unknown function. To systematically explore circRNAs, we sequenced and computationally analyzed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, with oftentimes tissue/developmental stage specific expression. Sequence analysis suggested important regulatory functions for circRNAs. Indeed, we discovered that human circRNA CDR1as is densely bound by miRNA effector complexes and harbors 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebra fish impaired midbrain development similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, indicating previously unrecognized regulatory potential of coding sequences. 1 Sample
Project description:Gemmatimonas phototrophica is the only phototrophic member of the recently discovered bacterial phylum Gemmatimonadetes. It was isolated from a freshwater lake in the Gobi desert and first described in 2014. So far, Gemmatimonas phototrophica is the only bacterium to have received a complete set of photosynthesis-related genes by horizontal gene transfer from an ancient phototrophic species from the phylum Proteobacteria. This organism illustrates the possibility for engineering phototrophic capability in a non-phototrophic organism and is therefore of great interest to the field of synthetic biology. The structure of the photosynthetic reaction center-light harvesting 1 complex is under investigation by cryo-EM. Proteomic analysis verified the identities of the expected protein components of this complex and, additionally revealed polypeptides that were previously undiscovered and could be mapped to the cryo-EM images.
Project description:This research examines animal teeth from Early Dynastic (2900-2350 BC) Mesopotamia (Southern Iraq) to assess animal management practices and identify consumption patterns in animal diets. The objective to answer larger questions about food management and environmental resilience in ancient early complex societies in the Near East was achieved by the use of mass spectrometry-based proteomics for dietary reconstruction. Dietary MS, a revolutionary new methodology applying proteomics techniques to archaeological sample sets to reconstruct ancient animal diet. A developed protein extraction technique followed by liquid chromatography tandem mass spectrometry allowed the identification of the specific plant species consumed in order to highlight variable herd management strategies, resource optimization, for each taxon over time. It also provided information on overall health and indications of disease. This is the first study to apply a full suite of analyses to the region and provides the foundations of a necessary long-term view of human interaction within an environment through both time and space.
Project description:Circular RNAs (circRNAs) in animals are an enigmatic class of RNAs with unknown function. To systematically explore circRNAs, we sequenced and computationally analyzed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, with oftentimes tissue/developmental stage specific expression. Sequence analysis suggested important regulatory functions for circRNAs. Indeed, we discovered that human circRNA CDR1as is densely bound by miRNA effector complexes and harbors 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebra fish impaired midbrain development similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, indicating previously unrecognized regulatory potential of coding sequences. PARCLIP was performed as in Hafner et. al Cell 2010 with HEK293 cell lines stably expressing HIS/FLAG/HA-tagged AGO1 or AGO2. We used 4-thiouridine (4SU) to enhance the crosslink and generated cDNA libraries.
Project description:The emergence of animal phyla, each with their unique body plan, was a rapid event in the history of animal life, yet its genomic underpinnings are still poorly understood. Here, we investigate at the genomic, regulatory, and cellular levels the origin of one of the most enigmatic animal phyla, the chaetognaths, whose distinctive organismal characteristics have historically complicated its phylogenetic placement. We show that some of these characteristics are reflected at the cell-type level by the expression of genes originating in the chaetognath lineage, contributing to adaptation to planktonic life at the sensory and structural levels. Chaetognaths belong to the gnathiferan lineage (also including rotifers and several other microscopic phyla), which is marked by accelerated genomic evolution with gene loss and chromosomal rearrangements. Chaetognaths further secondarily acquired thousands of newly duplicated genes, without evidence for a whole genome duplication, yielding, for instance, tandemly expanded Hox genes, as well as many phylum-specific genes. We also detected repeat-rich highly-methylated neocentromeres and a simplified DNA methylation toolkit, which is involved in mobile element repression rather than transcriptional control, a role inherited by trans-splicing. Consistent with fossil evidence, our observations suggest that chaetognaths emerged after a phase of morphological simplification through a reinvention of organ systems paralleled by massive genomic reorganisation, explaining the uniqueness of the chaetognath body plan.