Biology subjects

Dong, X.

Publications and source records attributed to Dong, X..

At least 253 records · Page 14Linked to original sources

bioRxiv2022

PP2A forestalls mitophagy by dephosphorylating Parkin and ubiquitin

Mitophagy is a selective autophagic process that removes damaged mitochondria. PINK1-Parkin axis is primarily responsible for initiating mitophagy via feedforward mechanism, in which PINK1 phosphorylates ubiquitin and Parkin, and Parkin gains E3 ligase activity at the mitochondrial outer membrane. However, the phosphatase of pParkin is unknown, and the braking mechanism of mitophagy is incomplete. Here we report that protein phosphatase 2A (PP2A) catalyzes the dephosphorylation of Parkin and ubiquitin, with C, A, and B55, the catalytic scaffolding and regulatory subunits, respectively. Up- or down-regulation of PP2A protein level in cells by over-expression or transfection of specific siRNA decreases or increases Parkin and ubiquitin phosphorylation levels, respectively. Consequently, PP2A phosphatase activity negatively modulates mitochondrial translocation of Parkin and forestalls mitophagy. Our finding thus places PP2A, an enzyme already known for its involvement in the pathogenesis of neurodegenerative diseases, further intertwined with the PINK1-Parkin signaling pathway.

biochemistry↗

bioRxiv2022

Single-cell Gene Regulation Network Interference by Large-scale Data Integration

Single-cell ATAC-seq (scATAC-seq) has proven to be a state-of-art approach to investigating gene regulation at the single-cell level. However, existing methods cannot precisely uncover cell-type-specific binding of transcription regulators (TRs) and construct gene regulation networks (GRNs) in single-cell. ChIP-seq has been widely used to profile TR binding sites in the past decades. Here, we developed SCRIP, an integrative method to infer single-cell TR activity and targets based on the integration of scATAC-seq and a large-scale TR ChIP-seq reference. Our method showed improved performance in evaluating TR binding activity compared to the existing motif-based methods and reached a higher consistency with matched TR expressions. Besides, our method enables identifying TR target genes as well as building GRNs at the single-cell resolution based on a regulatory potential model. We demonstrate SCRIPs utility in accurate cell-type clustering, lineage tracing, and inferring cell-type-specific GRNs in multiple biological systems. SCRIP is freely available at https://github.com/wanglabtongji/SCRIP.

bioinformatics↗

bioRxiv2022

A local translation program regulates centriole amplification in the airway epithelium

Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this, Tnrc6a loss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs. HighlightsO_LITnrc6a is expressed in the lung selectively in differentiating multiciliated cells (MCC) adjacent to centrioles. C_LIO_LITNRC6A localizes to apical granules containing AGO2, miRNAs and their targets, but lacking mRNA degradation enzymes. C_LIO_LITNRC6A granules are enriched in components of the mRNA translation machinery and show evidence of concentrated newly-synthesized proteins C_LIO_LILoss of Tnrc6a in the lung leads to reduction, not stabilization of miRNA targets. C_LIO_LITnrc6a is required for efficient centriole amplification and multicilia formation. C_LI

cell biology↗

bioRxiv2022

SELINA: Single-cell Assignment using Multiple-Adversarial Domain Adaptation Network with Large-scale References

The rapid accumulation of single-cell RNA-seq data has provided rich resources to characterize various human cell types. Cell type annotation is the critical step in analyzing single-cell RNA-seq data. However, accurate cell type annotation based on public references is challenging due to the inconsistent annotations, batch effects, and poor characterization of rare cell types. Here, we introduce SELINA (single cELl identity NAvigator), an integrative annotation transferring framework for automatic cell type annotation. SELINA optimizes the annotation for minority cell types by synthetic minority over-sampling, removes batch effects among reference datasets using a multiple-adversarial domain adaptation network (MADA), and fits the query data with reference data using an autoencoder. Finally, SELINA affords a comprehensive and uniform reference atlas with 1.7 million cells covering 230 major human cell types. We demonstrated the robustness and superiority of SELINA in most human tissues compared to existing methods. SELINA provided a one-stop solution for human single-cell RNA-seq data annotation with the potential to extend for other species.

bioinformatics↗

bioRxiv2022

Germline-soma Supply Mitochondria for mtDNA Inheritance in Mouse Oogenesis

Maternal transmission paradigm of mtDNA remains controversial in mammalian oogenesis. Germline-soma-to-oocyte communication by numerous transzonal nanotubes (TZTs) reminds whether intercellular mitochondrial transfer is associated with maternal inheritance. Here, we found that mouse oocytes egocentrically receive mitochondria via TZTs, which projected from germline-soma, to achieve 105 copies, instead of de novo synthesis of mtDNA subpopulation in growing oocytes. De novo assembled TZTs amongst germline-soma and oocytes accumulated mtDNA amounts of the oocytes in vitro. However, mitochondrial supplement from germline-soma gradually diminished along with oocyte growth and was terminated by meiosis resumption, in line with a decrease in the proportion of germline-soma with thriving mtDNA replication and FSH capture capability. Thus, germline-soma-to-oocyte mitochondrial transfer is responsible for mammalian mtDNA inheritance as well as oogenesis and aging. One-sentence summariesThe maternal mtDNA transmission accompanied by oogenesis is inseparable from germline-soma mitochondrial transport.

developmental biology↗

bioRxiv2022

SOX17 Is Not Required for the Derivation and Maintenance of Mouse Extraembryonic Endoderm Stem Cell Lines

Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm cell lineage. SOX17 is thought to be required for the derivation and maintenance of mouse XEN cell lines. Here we have re-evaluated this requirement for SOX17. We derived multiple SOX17-deficient XEN cell lines from preimplantation embryos of a SOX17-Cre knockout strain and chemically converted multiple SOX17-deficient embryonic stem cell lines into XEN cell lines by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of SOX17-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, SOX17 is not required for the derivation and maintenance of XEN cell lines.

developmental biology↗

bioRxiv2021

Rapid selection of P323L in the SARS-CoV-2 polymerase (NSP12) in humans and non-human primate models and confers a large plaque phenotype

The mutational landscape of SARS-CoV-2 varies at both the dominant viral genome sequence and minor genomic variant population. An early change associated with transmissibility was the D614G substitution in the spike protein. This appeared to be accompanied by a P323L substitution in the viral polymerase (NSP12), but this latter change was not under strong selective pressure. Investigation of P323L/D614G changes in the human population showed rapid emergence during the containment phase and early surge phase of wave 1 in the UK. This rapid substitution was from minor genomic variants to become part of the dominant viral genome sequence. A rapid emergence of 323L but not 614G was observed in a non-human primate model of COVID-19 using a starting virus with P323 and D614 in the dominant genome sequence and 323L and 614G in the minor variant population. In cell culture, a recombinant virus with 323L in NSP12 had a larger plaque size than the same recombinant virus with P323. These data suggest that it may be possible to predict the emergence of a new variant based on tracking the distribution and frequency of minor variant genomes at a population level, rather than just focusing on providing information on the dominant viral genome sequence e.g., consensus level reporting. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

microbiology↗

bioRxiv2021

Biological characteristics of two mesenchymal stem cell lines isolated from the umbilical cord and adipose tissue of a neonatal common hippo (Hippopotamus amphibius)

Mesenchymal stem cells (MSCs) are multipotent adult stem cells and can be isolated from many tissues of the body. Due to their potentials to treat various diseases and be applied in animal breeding, MSCs have been isolated and identified regarding their biological properties. Common hippos (Hippopotamus amphibius) are a vulnerable species and yet the cryopreservation of their genetic materials is scare. In this study, we successfully established two MSC lines (UC-MSCs and AT-MSCs) from the umbilical cord and adipose tissue of a neonatal common hippo and comparatively described their features. Both UC-MSCs and AT-MSCs showed fibroblastoid morphology and could be continuously passaged for over 17 passages without dramatic signs of senescence. The cell cultures had normal chromosome composition, say, 17 pairs of autosomes and 1 pair of X chromosomes. UC-MSCs and AT-MSCs displayed similar gene expression profiles. They were positive for CD45, CD73, CD90 and CD105 and negative for HLA-DR. They demonstrated stemness maintenance by expression of classical stem cell markers. UC-MSCs and AT-MSCs manifested different differentiation potentials into other cell lineages. In summary, these two cell lines demonstrated the essential properties of mesenchymal stem cells and might play a role in the future research.

cell biology↗

bioRxiv2021

High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effect

CRISPR-Cas13 systems have recently been employed for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has imposed a major barrier for their in vivo applications. We designed a dual-fluorescent reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells. Among over 200 engineered variants, several Cas13 variants (including Cas13d and Cas13X) exhibit efficient on-target activity but markedly reduced collateral activity. Furthermore, transcriptome-wide off-targets and cell growth arrest induced by Cas13 are absent for these variants. Importantly, high-fidelity Cas13 variants show comparable RNA knockdown activity with wild-type Cas13 but no detectable collateral damage in transgenic mice and adeno-associated virus-mediated somatic cell targeting. Thus, high-fidelity Cas13 variants with minimal collateral effect are now available for targeted degradation of RNAs in basic research and therapeutic applications.

molecular biology↗

bioRxiv2021

The Prion Protein Octarepeat Domain Forms Transient β-sheet Structures Upon Residue-Specific Cu(II) and Zn(II) Binding

Misfolding of the cellular prion protein (PrPC) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in the protein misfolding, and metal imbalance may be part of TSE pathologies. PrPC is a combined Cu(II) and Zn(II) metal binding protein, where the main metal binding site is located in the octarepeat (OR) region. Here, we used biophysical methods to characterize Cu(II) and Zn(II) binding to the isolated OR region. Circular dichroism (CD) spectroscopy data suggest that the OR domain binds up to four Cu(II) ions or two Zn(II) ions. Upon metal binding, the OR region seems to adopt a transient antiparallel {beta}-sheet hairpin structure. Fluorescence spectroscopy data indicates that under neutral conditions, the OR region can bind both Cu(II) and Zn(II) ions, whereas under acidic conditions it binds only Cu(II) ions. Molecular dynamics simulations suggest that binding of both metal ions to the OR region results in formation of {beta}-hairpin structures. As formation of {beta}-sheet structures is a first step towards amyloid formation, we propose that high concentrations of either Cu(II) or Zn(II) ions may have a pro-amyloid effect in TSEs.

biophysics↗

bioRxiv2021

A mixed blessing of viruses in wastewater treatment plants

Activated sludge of wastewater treatment plants harbors a very high diversity of both microorganisms and viruses, wherein the latter control microbial dynamics and metabolisms by infection and lysis of cells. However, it remains poorly understood how viruses impact the biochemical processes of activated sludge, for example in terms of treatment efficiency and pollutant removal. Using metagenomic and metatranscriptomic deep sequencing, the present study recovered thousands of viral sequences from activated sludge samples of three conventional wastewater treatment plants. Gene-sharing network indicated that most of viruses could not be assigned to known viral genera, implying activated sludge as an underexplored reservoir for new viruses and viral diversity. in silico Predictions of virus-host linkages demonstrated that infected microbial hosts, mostly belonging to bacteria, were transcriptionally active and able to hydrolyze polymers including starches, celluloses, and proteins. Some viruses encode auxiliary metabolic genes (AMGs) involved in carbon, nitrogen, and sulfur cycling, and antibiotic resistance genes (ARGs) for resistance to multiple drugs. The former group of virus-encoded genes (i.e. AMGs) may enhance the biodegradation of contaminants like starches and celluloses, suggesting a positive role for viruses in strengthening the performance of activated sludge. However, the latter group (i.e. ARGs) would be disseminated to different microorganisms using viruses as gene shuttles, demonstrating the possibility for viruses to facilitate the spread of antibiotic resistance in the environment. Collectively, this study highlights the mixed blessing of viruses in wastewater treatment plants, and deciphers how they manipulate the biochemical processes in the activated sludge, with implications for both environmental protection and ecosystem security.

microbiology↗

bioRxiv2021

Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2

HAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in Plasmodium have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of Plasmodium berghei HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of Plasmodium berghei in vitro and transmission of malaria in mosquitos. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the Plasmodium D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission.

immunology↗

bioRxiv2021

Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.

SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.

microbiology↗

bioRxiv2021

Preferential interactions of a crowder protein with the specific binding site of a native protein complex

The crowded cellular environments provide ample opportunities for proteins to interact with bystander macromolecules, yet direct evidence, let alone residue-specific information, for such nonspecific binding is rare. Here, by combining NMR spectroscopy and atomistic modeling, we investigated how crowders influence the association equilibrium and kinetics of two protein partners, EIN and HPr. Ficoll-70 increases the EIN-HPr binding affinity whereas bovine serum albumin (BSA) decreases the affinity. The opposite effects of the two crowders are quantitatively explained by atomistic modeling, which shows that the stabilizing effect of Ficoll-70 arises from volume exclusion favoring the bound state. In contrast, the destabilizing effect of BSA arises from preferential soft interactions with the free state; notably, BSA has favorable electrostatic interactions with positively charged HPr residues within the EIN-binding site. Some of the residues from this site indeed experience significant chemical shift perturbation when titrated with BSA, while the relaxation rates of HPr backbone amides exhibit overall elevation. Furthermore, relaxation dispersion data indicate that Ficoll-70 and BSA both slow down the EIN-HPr association rate, but change the dissociate rate in opposite directions. The observations on kinetics are accounted for by two effects of the crowders: increasing the solution microviscosity and reshaping the EIN-HPr interaction energy surface. The kind of preferential interactions between BSA and HPr that leads to competition with EIN should be prevalent in cellular environments. Our NMR results and atomistic modeling provide benchmarks, at both qualitative and quantitative levels, for the effects of crowded cellular environments on protein-protein specific interactions. Significance StatementAlthough nonspecific binding of crowder macromolecules with functional proteins is likely prevalent in vivo, direct evidence is rare. Here we present NMR characterizations showing that bovine serum albumin preferentially interacts with a specific binding site on HPr, leading to competition with the latters partner EIN. The preferential interactions result in destabilization of the EIN-HPr native complex and speedup of its dissociation, contrary to expectations from excluded-volume and viscosity effects. Atomistic modeling of macromolecular crowding rationalizes the experimental observations, and provides qualitative and quantitative insight into the influences of the crowded cellular environment on protein-protein specific interactions. Our work also has implications for evolution, regarding how nonspecific binding can be either minimized or exploited for gaining new functions.

biophysics↗

bioRxiv2021

Modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex with Microglia Containing Cerebral Organoids Derived from Induced Pluripotent Stem Cells

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS-PDC) is a neurodegenerative disease linked to the traditional consumption of cycad seeds by the Chamorro people of Guam. Little is known about the etiological role of cycad toxin in ALS-PDC. Patient-derived induced pluripotent stem cells were derived from age- and sex-matched affected and unaffected patient lymphoid cells then differentiated into cerebral organoids. After three months, the ALS-PDC affected organoids were smaller, their neurons had less extensive neurite outgrowth, and the organoids had more reactive astrocytes and M1 microglia, fewer resting and M2 microglia, and more open extracellular space. Most of these phenomena could be recapitulated by exposing unaffected organoids to {beta}-methylamino L-alanine (BMAA), a toxic amino acid produced by cyanobacteria living with cycad plants. Furthermore, ALS-PDC affected organoids exhibited an exacerbated neuroinflammatory response to BMAA exposure via activation of caspase1/NLRP3 inflammasome. A genome-wide transcriptome analysis of the organoids showed that the most down-regulated pathways were taurine, alanine, aspartate, and glutamate metabolism; protein digestion; and absorption. The most down-regulated biological processes were type I interferon signaling, regulation of neuron differentiation and extracellular matrix organization. Our results suggested that the etiology of ALS-PDC is due to metabolic disorders that shifted microglia to a more pro-inflammatory M1 state instead of a non-inflammatory, repairing M2 state, which exacerbated inflammation and reduced extracellular matrix strength. Supplementation of transforming growth factor beta (TGF-{beta}) to ALS-PDC affected organoids increased the expression of interferon-induced transmembrane proteins (IFITMs) and restored M2 microglia populations and extracellular matrix organization. Organoids containing networks of neurons, astrocytes, microglia derived from iPSC with our protocol provides an excellent cellular model for neurodegenerative disease modeling. Significance StatementO_LIWestern Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS-PDC) cerebral organoids containing networks of neurons, astrocytes, and microglia were generated from patient specific lymphoid derived induced pluripotent stem cells. C_LIO_LIALS-PDC affected organoids were smaller, with neurons had less extensive neurite outgrowth, more reactive astrocytes and M1 microglia, fewer resting and M2 microglia, and more open extracellular matrix spaces when compared to ALS-PDC unaffected organoids. C_LIO_LIGenome-wide transcriptome analysis indicated that ALS/PDC affected organoids had significantly lower expression of genes related to vitamin B6, amino acid and protein glycation metabolisms, down-regulated type I interferon signaling, the regulation of neuron differentiation and extracellular matrix production. C_LIO_LIOur results implicated that the etiology of ALS-PDC is due to metabolic disorders that led the shift of microglia to more pro-inflammatory M1 state and less non-inflammatory resting, repairing M2 state of microglia subpopulation, which primed the exacerbated inflammation and reduced extracellular matrix strength. TGF-{beta} promoted interferon-induced transmembrane protein (IFITMs) expression and restored the repairing M2 state of microglia population and extracellular matrix organization. C_LI

neuroscience↗

bioRxiv2021

Evolution of Plant Niche Construction Traits in Biogeomorphic Landscapes

By virtue of niche construction traits, plants play a significant role in shaping landscapes. The resultant outcome is a change in the selective environment, which influences the evolution of these same plants. So far almost all biogeomorphic models have assumed that niche construction traits are invariant in time. On the other hand, niche construction studies have assumed that independent abiotic changes are either nonexistent or are simply linear. Here, I considered the concomitant evolution of plant niche construction traits during landscape development. I constructed a geo-evolutionary model that couples a population genetic module with a landscape development module. Allowing plants to evolve always results in landforms different from those that appear when evolution is not accounted for. The topographic difference between cases with and without evolution ranges from a small difference in the steady-state topography, to drastic differences in landforms. The amount of difference is contingent upon forms of landscape development and the strength of geo-evolutionary coupling. Allowing the landscape to develop while evolution occurs changes evolutionary trajectories for niche construction traits. The landscape can even develop spatial structures that suppress selection. Model results clearly support the need to integrate niche construction theory and biogeomorphology to better understand both.

evolutionary biology↗

bioRxiv2021

Benchmarking UMI-based single cell RNA-sequencing preprocessing workflows

Single-cell RNA sequencing (scRNA-seq) technologies and associated analysis methods have undergone rapid development in recent years. This includes methods for data preprocessing, which assign sequencing reads to genes to create count matrices for downstream analysis. Several packaged preprocessing workflows have been developed that aim to provide users with convenient tools for handling this process. How different preprocessing workflows compare to one another and influence downstream analysis has been less well studied. Here, we systematically benchmark the performance of 9 end-to-end preprocessing workflows (Cell Ranger, Optimus, salmon alevin, kallisto bustools, dropSeqPipe, scPipe, zUMIs, celseq2 and scruff) using datasets with varying levels of biological complexity generated on the CEL-Seq2 and 10x Chromium platforms. We compare these workflows in terms of their quantification properties directly and their impact on normalization and clustering by evaluating the performance of different method combinations. We find that lowly expressed genes are discordant between workflows and observe that some workflows have systematic biases towards particular classes of genomics features. While the scRNA-seq preprocessing workflows compared varied in their detection and quantification of genes across datasets, after downstream analysis with performant normalization and clustering methods, almost all combinations produced clustering results that agreed well with the known cell type labels that provided the ground truth in our analysis. In summary, the choice of preprocessing method was found to be less influential than other steps in the scRNA-seq analysis process. Our study comprehensively compares common scRNA-seq preprocessing workflows and summarizes their characteristics to guide workflow users.

bioinformatics↗

bioRxiv2021

aCPSF1 in synergy with terminator U-tract dictates archaeal transcription termination efficiency via the KH domains recognizing U-tract

Recently, aCPSF1 was reported to function as the long-sought global transcription termination factor of archaea, while the working mechanism remains elusive. This work, through analyzing transcript-3'end-sequencing data of Methanococcus maripaludis, found positive correlations of both the terminator uridine(U)-tract and aCPSF1 with hierarchical transcription termination efficiencies (TTEs) at the genome-wide level. In vitro assays determined that aCPSF1 specifically binds to the terminator U-tract with U-tract number-related binding abilities, and in vivo assays demonstrated the two are indispensable in dictating high TTEs, revealing that aCPSF1 and the terminator U-tract in synergy determine high TTEs. The N-terminal KH domains equip aCPSF1 of specific binding to terminator U-tract and the in vivo aCPSF1-terminator U-tract synergism; aCPSF1s nuclease activity was also required for TTEs. aCPSF1 also functioned as back-up termination for transcripts with weak intrinsic terminator signals. aCPSF1 orthologs from Lokiarchaeota and Thaumarchaeota exhibited similar U-tract synergy in dictating TTEs. Therefore, aCPSF1 and the intrinsic U-rich terminator could work in a noteworthy two-in-one termination mode in Archaea, which could be widely employed by archaeal phyla; using one factor recognizing U-rich terminator signal and cleaving transcript 3'-end, the archaeal aCPSF1-dependent transcription termination could display a simplified archetypal mode of the eukaryotic RNA polymerase II termination machinery.

microbiology↗