Biology subjects

Shi, Q.

Publications and source records attributed to Shi, Q..

At least 109 records · Page 6Linked to original sources

bioRxiv2020

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2high/CKneg) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients. HK2high/CKneg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CKpos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

cancer biology↗

bioRxiv2020

Metabolic and functional impairment of CD8+ T cells from the lungs of influenza-infected obese mice

BackgroundObesity increases influenza disease risk in millions of adults worldwide. In this study, we investigated the effect of diet-induced obesity on pulmonary CD8+ T cell metabolism and function as a mechanism of impairment. MethodsMale C57BL/6J mice were fed either control (10% kcal/g) or high-fat (60% kcal/g) diet. Sub-lethal A/PR/8/34 influenza virus infection generated a robust pulmonary immune response. T cell metabolism and function were assessed at day 10 and day 24 post infection. ResultsAt day 10 post infection, CD8+ T cells from obese mice had impaired oxidative and glycolytic metabolism, greater fatty acid uptake, and decreased effector populations and cytokine production. At infection resolution, obese mice had lower numbers of naive and central memory CD8+ T cell populations in the lungs. ConclusionDiet-induced obesity increases influenza virus pathogenesis through CD8+ T cell mediated metabolic reprogramming resulting in suppressed effector CD8+ T cell function. SummaryDiet-induced obesity impairs the metabolism of pulmonary CD8+ T cells resulting in reduced effector CD8+ T cells and cytokine production following primary influenza infection.

immunology↗

bioRxiv2020

Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19

Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans. Bullet pointsO_LIWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19. C_LIO_LIACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. C_LIO_LIACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities. C_LIO_LIWe unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry. C_LI

cell biology↗

bioRxiv2020

A Heat-labile Enterotoxin B Subunit Mutant (LTB26) of Escherichia coli Enhances Mucosal Immune adjuvanticity via Increased BCR Activity

Although several SARS-COV-2 vaccines have been approved, no one oral live vaccine is available. Here, an oral SARS-COV-2 RBD live vaccine containing LTB26 adjuvant has been developed. BALB/c mice are oral vaccinated with attenuated Salmonella typhimurium SL7207 containing pcDNA3.1-LTB26RBD or pcDNA3.1-RBD plasmids. The result shows that the high level of RBD specific antibody is produced in pcDNA3.1- LTB26RBD treatment. The mechanism indicates that LTB26 enhances RBD antibody production by significantly upregulating the activity of MHC II+ DCs and CD19+CD45+ B cells. LTB26 mutant is derived from heat-labile enterotoxin B subunit (LTB) wild type of Escherichia coli with enhanced immune adjuvanticity. Based on the pre-experiment result that SL7207 interferes the function of LTB26, the purified LTB26 was mixed with purified human rotavirus VP8 antigen to explore the mechanism of adjuvant. The results suggests that LTB26 enhances mucosal immune responses via increased of BCR and MHC II+ expression. Furthermore, LTB26 promotes both Th1 and Th2 cell mediated immunity. Therefore, LTB26 maybe a potent adjuvant for mucosal vaccine development in view of the safety of LTB26 than LT toxin.

immunology↗

bioRxiv2020

Mechanisms of Action of Autophagy Modulators Dissected by Quantitative Systems Pharmacology Analysis

Autophagy plays an essential role in cell survival/death and functioning. Modulation of autophagy has been recognized as a promising therapeutic strategy against diseases/disorders associated with uncontrolled growth or accumulation of biomolecular aggregates, organelles or cells including those caused by cancer, aging, neurodegeneration, and liver diseases such as 1-antitrypsin deficiency. Numerous pharmacological agents that enhance or suppress autophagy have been discovered. However, their molecular mechanisms of action are far from clear. Here we collected a set of 225 autophagy modulators and carried out a comprehensive quantitative systems pharmacology (QSP) analysis of their targets using both existing databases and predictions made by our machine learning algorithm. Autophagy modulators include several highly promiscuous drugs (e.g. artenimol and olanzapine acting as activator, fostamatinib as inhibitor, or melatonin as dual-modulator), as well as selected drugs uniquely targeting specific proteins ([~]30% of modulators). They are mediated by three layers of regulation: (i) pathways involving core autophagy-related (ATG) proteins such as mTOR, AKT, and AMPK; (ii) upstream signaling events that regulates the activity of ATG pathways such as calcium-, cAMP-, and MAPK-signaling pathways; and (iii) transcription factors regulating the expression ATG proteins such as TFEB, TFE3, HIF-1, FoxO, and NF-{kappa}B. Our results suggest that PKA serves as a linker bridging between various signal transduction events and autophagy. These new insights contribute to a better assessment of the mechanism of action of autophagy modulators as well as their side effects, development of novel polypharmacological strategies, and identification of drug repurposing opportunities.

systems biology↗

bioRxiv2020

Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C

The gut microbiome harbors a silent reservoir of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through the process of horizontal gene transfer (HGT). To counteract the spread of AR genes, it is paramount to know which organisms harbor mobile AR genes and with which organisms they engage in HGT. Despite methods to characterize the bulk presence1, abundance2 and function3 of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) and their concomitant AR genes. Here, we apply and evaluate a high-throughput, culture-independent method for surveilling the bacterial carriage of MGEs, based on bacterial Hi-C protocols. We compare two healthy individuals with a cohort of seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics throughout their prolonged hospitalizations, and are thus acutely vulnerable to the threat of multidrug-resistant infections4. We find that the networks of HGT are surprisingly distinct between individuals, yet AR and mobile genes are more dispersed across taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT is occurring throughout the course of treatment in the microbiomes of neutropenic patients and within the guts of healthy individuals over a similar timeframe. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.

systems biology↗

bioRxiv2020

Coral accurately bridges paired-end RNA-seq reads alignment

MotivationThe established high-throughput RNA-seq technologies usually produce paired-end reads. A challenging problem is therefore to computationally infer the alignment of entire fragments given the alignment of the two mate ends. Solving this problem essentially provide longer RNA-seq reads, and hence benefits downstream RNA-seq analysis. ResultsWe introduce Coral, a new tool that can accurately bridge paired-end RNA-seq reads. The core of Coral is a novel optimization formulation that can capture the most reliable bridging path while also filter out false paths. An efficient dynamic programming algorithm is designed to calculate the top N optimum. Coral implements a consensus approach to select the best solution among the N candidates by taking into account the distribution of fragment length. Coral is modular, can be easily incorporated into existing RNA-seq analysis pipeline. We show that Coral can improve transcript assembly by a large margin: on average over 2377 RNA-seq samples from GTEx, the improvement (measured with adjusted precision) is 7.5% and 11.2% when Coral is incorporated with StringTie and Scallop, respectively. AvailabilityCoral is open-source, freely available at GitHub (https://github.com/Shao-Group/coral) and Bioconda. Scripts, datasets and documentations that can reproduce all experimental results in this paper are available at https://github.com/Shao-Group/coraltest.

bioinformatics↗

bioRxiv2019

Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation

Dosage compensation between the sexes has emerged independently multiple times during evolution, often harnessing long noncoding RNAs (lncRNAs) to alter gene expression on the sex chromosomes. In eutherian mammals, X chromosome inactivation (XCI) in females proceeds via the lncRNA Xist, which coats one of the two X chromosomes and recruits repressive proteins to epigenetically silence gene expression in cis1,2. How Xist evolved new functional RNA domains to recruit ancient, pleiotropic protein partners is of great interest. Here we show that Spen, an Xist-binding repressor protein essential for XCI3-7, binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen inactivation leads to de-repression of a subset of endogenous retroviral (ERV) elements in embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing8-9. ERV RNA and Xist A-repeat bind the RRM3 domain of Spen in a competitive manner. Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in local gene silencing in cis. These results suggest that insertion of an ERV element into proto-Xist may have been a critical evolutionary event, which allowed Xist to coopt transposable element RNA-protein interactions to repurpose powerful antiviral chromatin silencing machinery for sex chromosome dosage compensation.

genomics↗

bioRxiv2019

The natural compound Notopterol targets JAK2/3 to ameliorate macrophage-induced inflammation and arthritis

AbstractNotopterol (NOT) is one of the main constituents of the traditional Chinese medicinal herb Notopterygium incisum Ting ex H.T. Chang has anti-rheumatism activity, but the target of NOT remains unknown. Here we have demonstrated that orally or intraperitoneal administration of NOT exhibits significant therapeutic effects on the collagen-induced arthritis (CIA) model in both DBA/1J and C57/BL6 mice. NOT treatment in vivo and in vitro reduces production of inflammatory cytokines and chemokines in TNF- or LPS/IFN{gamma}-stimulated macrophages via blocking the JAK2/3-STAT3/5 activation. Mechanistically, NOT directly binds JAK2 to inhibit its activity via Arg980, Asn981, and Leu932 in the JH1 domain. Importantly, expression of the L938A/R980A/N981A mutant in zebrafish significantly inhibited the in vivo inflammatory response after LPS injection, which showed no further inhibitory effect upon NOT treatment. Combination of NOT and an anti-TNF antibodies could achieve a better therapeutic effect than anti-TNF alone in the CIA model. We therefore suggest that as a specific JAK2/3 inhibitor, the natural compound NOT ameliorates pathology of RA, which might be useful to treat other JAK2/3-related diseases.

immunology↗

bioRxiv2019

Purification, identification, and characterization of two benzophenanthridine alkaloids from Corydalis longicalcarata rhizomes with anti-mitotic and polyploidy-inducing activities

Mitosis has long been a therapeutic target for the treatment of cancer. After conducting a phenotypic screen for anti-mitotic activity in a crude extract library of more than 2000 medicinal plants, we identified the rhizomes of Corydalis longicalcarata. Guided by the bioactivity-based assay, two benzophenanthridine alkaloids were purified and subsequently identified as corynoline and its close analog acetylcorynoline. This study uncovers a previously unknown antimitotic activity for these two phytochemicals, discovers their potential to be developed as anticancer drugs, and highlights their pleiotropic effects on cell division, including prevention of chromosome congression, compromise of spindle checkpoint response, and blockage of cytokinesis.

cancer biology↗

bioRxiv2019

A portable and cost-effective microfluidic system for massively parallel single-cell transcriptome profiling

Single-cell technologies are becoming increasingly widespread and have been revolutionizing our understanding of cell identity, state, diversity and function. However, current platforms can be slow to apply to large-scale studies and resource-limited clinical arenas due to a variety of reasons including cost, infrastructure, sample quality and requirements. Here we report DNBelab C4 (C4), a negative pressure orchestrated, portable and cost-effective device that enables high-throughput single-cell transcriptional profiling. C4 system can efficiently allow discrimination of species-specific cells at high resolution and dissect tissue heterogeneity in different organs, such as murine lung and cerebral cortex. Finally, we show that the C4 system is comparable to existing platforms but has huge benefits in cost and portability and, as such, it will be of great interest for the wider scientific community.

genomics↗

bioRxiv2019

A high-content screen identifies the vulnerability of MYC-overexpressing cells to dimethylfasudil

A synthetic lethal effect arises when a cancer-associated change introduces a unique vulnerability to cancer cells that makes them unusually susceptible to a drugs inhibitory activity. The synthetic lethal approach is attractive because it enables targeting of cancers harboring specific genomic alterations, the products of which may have proven refractory to direct targeting. An example is cancer driven by overexpression of MYC. Here, we conducted a high-content screen for compounds that are synthetic lethal to elevated MYC using a small-molecule library to identify compounds that are closely related to, or are themselves, regulatory-approved drugs. The screen identified dimethylfasudil, a potent and reversible inhibitor of Rho-associated kinases ROCK1 and ROCK2. Close analogs of dimethylfasudil are used clinically to treat neurologic and cardiovascular disorders. The synthetic lethal interaction was conserved in rodent and human cell lines and could be observed with activation of either MYC or its paralog MYCN. The synthetic lethality seems specific to MYC overexpressing cells as it could not be substituted by a variety of oncogenic manipulations and synthetic lethality was diminished by RNAi-mediated depletion of MYC in human cancer cell lines. Collectively, these data support investigation of the use of dimethylfasudil as a drug that is synthetic lethal for malignancies that specifically overexpress MYC.\n\nSignificance StatementSynthetic lethal targeting of tumors overexpressing MYC holds promise for attacking aggressive malignancies. Here we describe a synthetic lethal interaction between dimethylfasudil and overexpression of MYC. Uniquely, this novel synthetic lethal interaction points toward an opportunity for synthetic lethality with a molecule likely to harbor favorable drug-like properties that enable systemic use.

cancer biology↗

bioRxiv2019

Single-cell transcriptome profiling reveals neutrophil heterogeneity and orchestrated maturation during homeostasis and bacterial infection

The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function, and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets. Driven by both known and uncharacterized transcription factors, neutrophils gradually acquire microbicidal capability as they traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall heterogeneity. In summary, these data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers, and therapeutic targets at single-cell resolution.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC=\"FIGDIR/small/792200v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@18fed35org.highwire.dtl.DTLVardef@1e68b7org.highwire.dtl.DTLVardef@6cfbc8org.highwire.dtl.DTLVardef@1061a26_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA comprehensive single-cell resolution transcriptional landscape of mouse neutrophil maturation and fate decision under steady-state and bacterial infection conditions.\nC_LIO_LIThe pathogen clearance machinery in neutrophils is continuously and gradually built during neutrophil differentiation, maturation, and aging, driven by both known and uncharacterized transcription factors.\nC_LIO_LIThe three mature neutrophil subsets in peripheral blood, including a novel ISG-expressing subset, are derived from distinct bone marrow neutrophil precursors.\nC_LIO_LIBacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall neutrophil heterogeneity.\nC_LIO_LIBacterial infection-induced emergency granulopoiesis is mediated by augmented proliferation of early stage neutrophil progenitors and accelerated post-mitotic maturation.\nC_LI

immunology↗

bioRxiv2019

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

Drug-induced dedifferentiation towards a drug-tolerant persister state is a common mechanism cancer cells exploit to escape therapies, posing a significant obstacle to sustained therapeutic efficacy. The dynamic coordination of epigenomic and transcriptomic programs at the early-stage of drug exposure, which initiates and orchestrates these reversible dedifferentiation events, remains largely unexplored. Here we employ high-temporal-resolution multi-omics profiling, information-theoretic approaches, and dynamic system modeling to probe these processes in BRAF-mutant melanoma models and patient specimens. We uncover a hysteretic transition trajectory of melanoma cells in response to oncogene inhibition and subsequent release, driven by the sequential operation of two tightly coupled transcriptional waves, which orchestrate genome-scale chromatin state reconfiguration. Modeling of the transcriptional wave interactions predicts NF-{kappa}B/RelA-driven chromatin remodeling as the underlying mechanism of cell-state dedifferentiation, a finding we validate experimentally. Our results identify critical RelA-target genes that are epigenetically modulated to drive this process, establishing a quantitative epigenome gauge to measure cell-state plasticity in melanomas, which supports the potential use of drugs targeting epigenetic machineries to potentiate oncogene inhibition. Extending our investigation to other cancer models, we identify oxidative stress-mediated NF-{kappa}B/RelA activation as a common mechanism driving cellular transitions towards drug-tolerant persister states, revealing a novel and pivotal role for the NF-{kappa}B signaling axis in linking cellular oxidative stress to cancer progression.

cancer biology↗

bioRxiv2019

Identification of \"Missing Link\" Families of Small DNA Tumor Viruses

Polintons (also known as Mavericks) were initially identified as a widespread class of eukaryotic transposons named for their hallmark type B DNA polymerase and retrovirus-like integrase genes. It has since been recognized that many polintons encode possible capsid proteins and viral genome-packaging ATPases similar to those of a diverse range of double-stranded DNA (dsDNA) viruses. This supports the inference that at least some polintons are viruses that remain capable of cell-to-cell spread. At present, there are no polinton-associated capsid protein genes annotated in public sequence databases. To rectify this deficiency, we used a data-mining approach to investigate the distribution and gene content of polinton-like elements and related DNA viruses in animal genomic and metagenomic sequence datasets. The results define a discrete family-like clade of animal-specific viruses with two genus-level divisions. We suggest the family name Adintoviridae, connoting similarities to adenovirus virion proteins and the presence of a retrovirus-like integrase gene. Although adintovirus-class PolB sequences were detected in datasets for fungi and various unicellular eukaryotes, sequences resembling adintovirus virion proteins and accessory genes appear to be restricted to animals. Degraded adintovirus sequences are endogenized into the germlines of a wide range of animals, including humans.

microbiology↗

bioRxiv2019

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin1/Atg6-mediated lethal autophagy in polyploid cells

Inhibition of Aurora-B kinase is a synthetic lethal therapy for tumors that overexpress the MYC oncoprotein. It is currently unclear whether co-occurring oncogenic alterations might influence this synthetic lethality by confering more or less potency in the killing of tumor cells. To identify such modifers, we utilized isogenic cell lines to test a variety of cancer genes that have been previously demonstrated to promote survival under conditions of cellular stress, contribute to chemoresistance and/or suppress MYC-primed apoposis. We found that Bcl-2 and Bcl-xL, two antiapoptotic members of the Bcl-2 family, can partially suppress the synthetic lethality, but not multinucleation, elicited by a panaurora kinase inhibitor, VX-680. We demonstrate that this suppression stems from the rescue of autophagic cell death, specifically of multinucleated cells, rather than a general inhibition of apoptosis. Bcl-2 inhibits VX-680-induced death of polyploid cells by interacting with the autophagy protein Beclin1/Atg6 and rescue requires localization of Bcl-2 to the endoplasmic reticulum. These findings expand on previous conclusions that autophagic death of polyploid cells is mediated by Atg6. Bcl-2 and Bcl-xL negatively modulate MYC-VX-680 synthetic lethality and it is the anti-autophagic activity of these two Bcl-2 family proteins, specifically in multinucleate cells, that contributes to resistance to Aurora kinase-targeting drugs.

cancer biology↗

bioRxiv2019

β-blockers augment L-type Ca2+ channel activity by target-selective spatially restricted β2AR-cAMP-PKA signaling in neurons

G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in mammalian cells. Here, we report that some antagonists of {beta} adrenergic receptors ({beta}ARs) such as {beta}-blocker carvedilol and alprenolol activate {beta}2AR at nanomolar concentrations, which promote G protein signaling and cAMP/PKA activity without action of G protein receptor kinases (GRKs). The cAMP/PKA signal is restricted within the local plasma membrane domain, leading to selectively enhance PKA-dependent augment of endogenous L-type calcium channel (LTCC) activity but not AMPA receptor in hippocampal neurons. Moreover, we have engineered a mutant {beta}2AR that lacks serine 204 and 207 in the catecholamine binding pocket. This mutant can be preferentially activated by carvedilol but not the orthosteric agonist isoproterenol. Carvedilol activates the mutant {beta}2AR in hippocampal neurons augmenting LTCC activity through cAMP/PKA signaling. Together, our study identifies a mechanism by which {beta}-blocker-dependent activation of GPCRs at low ligand concentrations promotes local cAMP/PKA signaling to selectively target membrane downstream effectors such as LTCC in neurons.

cell biology↗

bioRxiv2019

The identification of mecciRNAs and their roles in mitochondrial entry of proteins

Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by nuclear genome have to be imported from the cytosol into the mitochondria. Here we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components of mitochondrial protein and RNA importation such as TOM40 and PNPASE interact with mecciRNAs and regulate protein entry. Expression of mecciRNAs is regulated, and these transcripts are critical for mitochondria in adapting to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to eukaryotic circular RNAs, and shed novel lights on communication between mitochondria and nucleus.

molecular biology↗