Evolutionary dynamics of circular RNAs in primates.
Ontology highlight
ABSTRACT:
SUBMITTER: Santos-Rodriguez G
PROVIDER: S-EPMC8516421 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Evolutionary dynamics of circular RNAs in primates.
Santos-Rodriguez Gabriela G Voineagu Irina I Weatheritt Robert J RJ
eLife 20210920
Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions ...[more]
Similar Datasets
Project description:Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, caspase-5, caspase-11, and caspase-12 and CARD16, 17, and 18) each have unique evolutionary trajectories. Caspase-4 is found across simian primates, whereas we identified multiple pseudogenization and gene loss events in caspase-5, caspase-11, and the CARDs. Because caspase-4 and caspase-11 are both key players in the noncanonical inflammasome pathway, we expected that these proteins would be likely to evolve rapidly. Instead, we found that these two proteins are largely conserved, whereas caspase-4's close paralog, caspase-5, showed significant indications of positive selection, as did primate caspase-1. Caspase-12 is a nonfunctional pseudogene in humans. We find this extends across most primates, although many rodents and some primates retain an intact, and likely functional, caspase-12. In mouse laboratory lines, we found that 50% of common strains carry nonsynonymous variants that may impact the functions of caspase-11 and caspase-12 and therefore recommend specific strains to be used (and avoided). Finally, unlike rodents, primate caspases have undergone repeated rounds of gene conversion, duplication, and loss leading to a highly dynamic proinflammatory caspase repertoire. Thus, we uncovered many differences in the evolution of primate and rodent proinflammatory caspases and discuss the potential implications of this history for caspase gene functions.
| S-EPMC11630849 | biostudies-literature
Project description:Circular RNAs (circRNAs) have been recognized as critical regulators of skeletal muscle development. Myocyte enhancer factor 2A (MEF2A) is an evolutionarily conserved transcriptional factor that regulates myogenesis. However, it remains unclear whether MEF2A produces functional circRNAs. In this study, we identified two evolutionarily conserved circular MEF2A RNAs (circMEF2As), namely circMEF2A1 and circMEF2A2, in chicken and mouse muscle stem cells. Our findings revealed that circMEF2A1 promotes myogenesis by regulating the miR-30a-3p/PPP3CA/NFATC1 axis, whereas circMEF2A2 facilitates myogenic differentiation by targeting the miR-148a-5p/SLIT3/ROBO2/β-catenin signaling pathway. Furthermore, in vivo experiments demonstrated that circMEF2As both promote skeletal muscle growth. We also discovered that the linear MEF2A mRNA-derived MEF2A protein binds to its own promoter region, accelerating the transcription of MEF2A and upregulating the expression of both linear MEF2A and circMEF2As, forming a MEF2A autoregulated positive feedback loop. Moreover, circMEF2As positively regulate the expression of linear MEF2A by adsorbing miR-30a-3p and miR-148a-5p, which directly contribute to the MEF2A autoregulated feedback loop. Importantly, we found that mouse circMEF2As are essential for the myogenic differentiation of C2C12 cells. Collectively, our results demonstrated the evolution, function, and underlying mechanisms of circMEF2As in animal myogenesis, which may provide novel insight for both the farm animal meat industry and human medicine.
| S-EPMC10508632 | biostudies-literature
Project description:Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, -5, -11, -12, and CARD16, 17, and 18) each have unique evolutionary trajectories. Caspase-4 is found across simian primates, whereas we identified multiple pseudogenization and gene loss events in caspase-5, caspase-11, and the CARDs. Because caspases-4 and -11 are both key players in the non-canonical inflammasome pathway, we expected that these proteins would be likely to evolve rapidly. Instead, we found that these two proteins are largely conserved, whereas caspase-4's close paralog, caspase-5, showed significant indications of positive selection, as did primate caspase-1. Caspase-12 is a non-functional pseudogene in humans. We find this extends across most primates, although many rodents and some primates retain an intact, and likely functional, caspase-12. In mouse laboratory lines, we found that 50% of common strains carry non-synonymous variants that may impact the functions of caspase-11 and -12, and therefore recommend specific strains to be used (and avoided). Finally, unlike rodents, primate caspases have undergone repeated rounds of gene conversion, duplication, and loss leading to a highly dynamic pro-inflammatory caspase repertoire. Thus we uncovered many differences in the evolution of primate and rodent pro-inflammatory caspases, and discuss the potential implications of this history for caspase gene functions.
| S-EPMC11383037 | biostudies-literature
Project description:POTE (prostate, ovary, testis, and placenta expressed) genes belong to a primate-specific gene family expressed in prostate, ovary, and testis as well as in several cancers including breast, prostate, and lung cancers. Due to their tumor-specific expression, POTEs are potential oncogenes, therapeutic targets, and biomarkers for these malignancies. This gene family maps within human and primate segmental duplications with a copy number ranging from two to 14 in different species. Due to the high sequence identity among the gene copies, specific efforts are needed to assemble these loci in order to correctly define the organization and evolution of the gene family. Using single-molecule, real-time (SMRT) sequencing, in silico analyses, and molecular cytogenetics, we characterized the structure, copy number, and chromosomal distribution of the POTE genes, as well as their expression in normal and disease tissues, and provided a comparative analysis of the POTE organization and gene structure in primate genomes. We were able, for the first time, to de novo sequence and assemble a POTE tandem duplication in marmoset that is misassembled and collapsed in the reference genome, thus revealing the presence of a second POTE copy. Taken together, our findings provide comprehensive insights into the evolutionary dynamics of the primate-specific POTE gene family, involving gene duplications, deletions, and long interspersed nuclear element (LINE) transpositions to explain the actual repertoire of these genes in human and primate genomes.
| S-EPMC7073761 | biostudies-literature
Project description:Chilling stress threatens the yield and distribution pattern of global crops, including the tea plant (Camellia sinensis), one of the most important cash crops around the world. Circular RNA (circRNA) plays roles in regulating plant growth and biotic/abiotic stress responses. Understanding the evolutionary characteristics of circRNA and its feedbacks to chilling stress in the tea plant will help to elucidate the vital roles of circRNAs. In the current report, we systematically identified 2702 high-confidence circRNAs under chilling stress in the tea plant, and interestingly found that the generation of tea plant circRNAs was associated with the length of their flanking introns. Repetitive sequences annotation and DNA methylation analysis revealed that the longer flanking introns of circRNAs present more repetitive sequences and higher methylation levels, which suggested that repeat-elements-mediated DNA methylation might promote the circRNAs biogenesis in the tea plant. We further detected 250 differentially expressed circRNAs under chilling stress, which were functionally enriched in GO terms related to cold/stress responses. Constructing a circRNA-miRNA-mRNA interaction network discovered 139 differentially expressed circRNAs harboring potential miRNA binding sites, which further identified 14 circRNAs that might contribute to tea plant chilling responses. We further characterized a key circRNA, CSS-circFAB1, which was significantly induced under chilling stress. FISH and silencing experiments revealed that CSS-circFAB1 was potentially involved in chilling tolerance of the tea plant. Our study emphasizes the importance of circRNA and its preliminary role against low-temperature stress, providing new insights for tea plant cold tolerance breeding.
| S-EPMC9861842 | biostudies-literature
Project description:Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) cause ∼2% of all human cancers. RNase R-resistant RNA sequencing revealed that both gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV abundantly expressed both exon-only and exon-intron circRNAs from the BamHI A rightward transcript (BART) locus (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA region. The circBARTs were expressed in all verified EBV latency types, including EBV-positive posttransplant lymphoproliferative disease, Burkitt lymphoma, nasopharyngeal carcinoma, and AIDS-associated lymphoma tissues and cell lines. Only cells infected with the B95-8 EBV strain, with a 12-kb BART locus deletion, were negative for EBV circBARTs. Less abundant levels of EBV circRNAs originating from LMP2- and BHLF1-encoding genes were also identified. The circRNA sequencing of KSHV-infected primary effusion lymphoma cells revealed a KSHV-encoded circRNA from the vIRF4 locus (circvIRF4) that was constitutively expressed. In addition, KSHV polyadenylated nuclear (PAN) RNA locus generated a swarm (>100) of multiply backspliced, low-abundance RNase R-resistant circRNAs originating in both sense and antisense directions consistent with a novel hyperbacksplicing mechanism. In EBV and KSHV coinfected cells, exon-only EBV circBARTs were located more in the cytoplasm, whereas the intron-retaining circBARTs were found in the nuclear fraction. KSHV circvIRF4 and circPANs were detected in both nuclear and cytoplasmic fractions. Among viral circRNAs tested, none were found in polysome fractions from KSHV-EBV coinfected BC1 cells, although low-abundance protein translation from viral circRNAs could not be excluded. The circRNAs are a new class of viral transcripts expressed in gammaherpesvirus-related tumors that might contribute to viral oncogenesis.
| S-EPMC6140489 | biostudies-literature
Project description:As an emerging class of RNA molecules, circular RNAs play pivotal roles in various biological processes, thereby determining their three-dimensional (3D) structure is crucial for a deep understanding of their biological significances. Similar to linear RNAs, the development of computational methods for circular RNA 3D structure prediction is challenging, especially considering the inherent flexibility and potentially long length of circular RNAs. Here, we introduce an extension of our previous IsRNA2 model, named IsRNAcirc, to enable circular RNA 3D structure predictions through coarse-grained molecular dynamics simulations. The workflow of IsRNAcirc consists of four main steps, including input preparation, end closure, structure prediction, and model refinement. Our results demonstrate that IsRNAcirc can provide reasonable 3D structure predictions for circular RNAs, which significantly reduce the locally irrational elements contained in the initial input. Moreover, for a validation test set comprising 34 circular RNAs, our IsRNAcirc can generate 3D models with better scores than the template-based 3dRNA method. These findings demonstrate that our IsRNAcirc method is a promising tool to explore the structural details along with intricate interactions of circular RNAs.
| S-EPMC11542809 | biostudies-literature
Project description:Small RNAs (sRNAs) are widespread in bacteria and play critical roles in regulating physiological processes. They are best characterized in Escherichia coli K-12 MG1655, where 83 sRNAs constitute nearly 2% of the gene complement. Most sRNAs act by base pairing with a target mRNA, modulating its translation and/or stability; many of these RNAs share only limited complementarity to their mRNA target, and require the chaperone Hfq to facilitate base pairing. Little is known about the evolutionary dynamics of bacterial sRNAs. Here, we apply phylogenetic and network analyses to investigate the evolutionary processes and principles that govern sRNA gene distribution in 27 E. coli and Shigella genomes. We identify core (encoded in all 27 genomes) and variable sRNAs; more than two-thirds of the E. coli K-12 MG1655 sRNAs are core, whereas the others show patterns of presence and absence that are principally due to genetic loss, not duplication or lateral genetic transfer. We present evidence that variable sRNAs are less tightly integrated into cellular genetic regulatory networks than are the core sRNAs, and that Hfq facilitates posttranscriptional cross talk between the E. coli-Shigella core and variable genomes. Finally, we present evidence that more than 80% of genes targeted by Hfq-associated core sRNAs have been transferred within the E. coli-Shigella clade, and that most of these genes have been transferred intact. These results suggest that Hfq and sRNAs help integrate laterally acquired genes into established regulatory networks.
| S-EPMC3318445 | biostudies-literature
Project description:Abstract Bladder cancer (BC) is the most common urinary system malignancy and is a serious threat to human health. Circular RNAs (circRNAs) are members of a newly defined class of noncoding RNAs (ncRNAs) that can regulate gene expression at the transcriptional or posttranscriptional level. Studies have shown that circRNAs are related to the clinicopathological characteristics, prognosis, and chemosensitivity of BC, and basic research has further confirmed that changes in the expression of circRNAs in BC are closely related to various tumor biological functions. CircRNAs promote tumor development by interacting with miRNAs to regulate transcription factors and both classical and nonclassical tumor signaling pathways. The nonclassical signaling pathways are related to cell cycle progression, epithelial–mesenchymal transition (EMT), extracellular matrix maintenance, and tumor stem cell maintenance. In this article, the relationships between circRNAs and the clinical characteristics of BC are reviewed, and the molecular mechanisms by which circRNAs promote tumor development are explored.
| S-EPMC7535116 | biostudies-literature
Project description:The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations. In this study, we explored the regulation of a novel class of RNAs, circular RNAs (circRNAs), by the addictive opioid heroin in the rat orbitofrontal cortex (OFC), a brain region that mediates behavioral responses to rewarding stimuli. Microarray analysis identified 76 OFC circRNAs significantly regulated in male rats after heroin self-administration. We evaluated the specificity of these findings by measuring heroin-associated circRNA expression in female rats after heroin self-administration and in rats that self-administered sucrose. We identify circGrin2b, circUbe2cp, circAnks1a, circAdcy5 and circSlc24A2 as heroin-responsive circRNAs in the OFC. Linear mRNA levels of heroin-associated circRNAs were unchanged except for Grin2b and Adcy5. An integrated bioinformatics analysis of regulated circRNAs identified microRNAs predicted to bind heroin-associated circRNAs and downstream targets of circRNA: microRNA sponging. Thus, heroin regulates the expression of OFC RNA splice variants that circularize and may impact cellular processes that contribute to the neurobiological adaptations that arise from chronic heroin exposure.
| S-EPMC8836038 | biostudies-literature