Germ granule compartments coordinate specialized small RNA production.

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5' regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.

Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after transient early-life heat stress. Such regulation requires CBP-1, a histone acetyltransferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.

Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer.

Natural selection drives the acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisitions in immunity, metabolic, and reproduction function via interdomain HGT (iHGT) from bacteria. Here, we report that the nematode gene rml-3 has been acquired by iHGT from bacteria and that it enables exoskeleton resilience and protection against environmental toxins in Caenorhabditis elegans. Phylogenetic analysis reveals that diverse nematode RML-3 proteins form a single monophyletic clade most similar to bacterial enzymes that biosynthesize L-rhamnose, a cell-wall polysaccharide component. C. elegans rml-3 is highly expressed during larval development and upregulated in developing seam cells upon heat stress and during the stress-resistant dauer stage. rml-3 deficiency impairs cuticle integrity, barrier functions, and nematode stress resilience, phenotypes that can be rescued by exogenous L-rhamnose. We propose that interdomain HGT of an ancient bacterial rml-3 homolog has enabled L-rhamnose biosynthesis in nematodes, facilitating cuticle integrity and organismal resilience to environmental stressors during evolution. These findings highlight a remarkable contribution of iHGT on metazoan evolution conferred by the domestication of a bacterial gene.

A single-cell landscape of pre- and post-menopausal high-grade serous ovarian cancer ascites.

High-grade serous ovarian cancer (HGSOC) is a hormone-related cancer with high mortality and poor prognosis. Based on the transcriptome of 57,444 cells in ascites from 10 patients with HGSOC (including 5 pre-menopausal and 5 post-menopausal patients), we identified 14 cell clusters which were further classified into 6 cell types, including T cells, B cells, NK cells, myeloid cells, epithelial cells, and stromal cells. We discovered an increased proportion of epithelial cells and a decreased proportion of T cells in pre-menopausal ascites compared with post-menopausal ascites. GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

Acquired stress resilience through bacteria-to-nematode horizontal gene transfer.

Natural selection drives acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisition of functions in immunity, metabolism, and reproduction via interdomain HGT (iHGT) from bacteria. We report that the nematode gene rml-3, which was acquired by iHGT from bacteria, enables exoskeleton resilience and protection against environmental toxins in C. elegans. Phylogenetic analysis reveals that diverse nematode RML-3 proteins form a single monophyletic clade most highly similar to bacterial enzymes that biosynthesize L-rhamnose to build cell wall polysaccharides. C. elegans rml-3 is regulated in developing seam cells by heat stress and stress-resistant dauer stage. Importantly, rml-3 deficiency impairs cuticle integrity, barrier functions and organismal stress resilience, phenotypes that are rescued by exogenous L-rhamnose. We propose that iHGT of an ancient bacterial rml-3 homolog enables L-rhamnose biosynthesis in nematodes that facilitates cuticle integrity and organismal resilience in adaptation to environmental stresses during evolution. These findings highlight the remarkable contribution of iHGT on metazoan evolution that is conferred by the domestication of bacterial genes.

rRNA intermediates coordinate the formation of nucleolar vacuoles in C. elegans.

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C. elegans. Type I nucleoli are spherical and do not have visible nucleolar vacuoles (NoVs), and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. Type II nucleoli contain vacuoles, and rRNA transcription and processing factors exclusively accumulate in the periphery rim. The NoV contains nucleoplasmic proteins and is capable of exchanging contents with the nucleoplasm. The high-order structure of the nucleolus is dynamically regulated in C. elegans. Faithful rRNA processing is important to prohibit NoVs. The depletion of 27SA2 rRNA processing factors resulted in NoV formation. The inhibition of RNA polymerase I (RNAPI) transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of NoVs. This finding provides a mechanism to coordinate structure maintenance and gene expression.

Experimental Study on Drying Biomass with a Spherical Heat Carrier.

Due to the reduction of the thermal efficiency and output fluctuation of the boiler system caused by the high moisture in biomass, dewatering of fuels using low-cost processes is an important step in feedstock pretreatment for biomass power plants. In the present study, a steel ball was used as the spherical heat carrier (SHC). The effects of the SHC temperature on the dewatering of different biomasses were investigated by a mixture-drying device at 40% moisture content of biomass, and the drying process of peanut shells was analyzed. Results showed that the moisture content was effectively reduced, and the combustion performance of the biomass was significantly promoted. The work is likely to provide an economically feasible approach for biomass drying in further studies.

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. The up-regulation of TSP-1 persists even after transient early-life stress. Such regulation requires CBP-1, a histone acetyl-transferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.

Nitrogen addition increases topsoil carbon stock in an alpine meadow of the Qinghai-Tibet Plateau.

Soil carbon (C) sequestration plays a critical role in mitigating climate change. Nitrogen (N) deposition greatly affects soil C dynamics by altering C input and output. However, how soil C stocks respond to various forms of N input is not well clear. This study aimed to explore the impact of N addition on soil C stock and to elucidate the underlying mechanisms in an alpine meadow on the eastern Qinghai-Tibet Plateau. The field experiment involved three N application rates and three N forms, using a non-N treatment as a control. After six years of N addition, the total C (TC) stocks in the topsoil (0-15 cm) were markedly increased by an average of 12.1 %, with a mean annual rate of 20.1 ‰, and no difference was found between the N forms. Irrespective of rate or form, N addition significantly increased the topsoil microbial biomass C (MBC) content, which was positively correlated with mineral-associated and particulate organic C content and was identified as the most important factor that affecting the topsoil TC. Meanwhile, N addition significantly increased the aboveground biomass in the years with moderate precipitation and relatively high temperature, which leads to higher C input into soils. Owing to decreased pH and/or activities of ß-1,4-glucosidase (ßG) and cellobiohydrolase (CBH) in the topsoil, organic matter decomposition was most likely inhibited by N addition, and this inhibiting effect varied under different N forms. Additionally, TC content in the topsoil and subsoil (15-30 cm) exhibited parabolic and positive linear relationship with the topsoil dissolved organic C (DOC) content, respectively, indicating that DOC leaching might be an important influencing factor for soil C accumulation. These findings improve our understanding of how N enrichment affects C cycles in alpine grassland ecosystems and suggest that soil C sequestration in alpine meadows probably increases with N deposition.

Regulating the Size of Simvastatin-loaded Discoidal Reconstituted Highdensity Lipoprotein: Preparation, Characterization, and Investigation of Cellular Cholesterol Efflux.

BACKGROUND: Reverse cholesterol transportation is essential for high-density lipoprotein (HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that particle size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs (rHDLs) possess a similar function to natural ones. OBJECTIVE: The study aimed to investigate the effect of particle size on the cholesterol efflux capacity of discoidal rHDLs and whether drug loadings may have an influence on this effect. METHODS: Different-sized simvastatin-loaded discoidal rHDLs (ST-d-rHDLs) resembling nascent HDL were prepared by optimizing key factors related to the sodium cholate of film dispersion-sodium cholate dialysis method with a single controlling factor. Their physicochemical properties, such as particle size, zeta potential, and morphology in vitro, were characterized, and their capacity of cellular cholesterol efflux in foam cells was evaluated. RESULTS: We successfully constructed discoidal ST-d-rHDLs with different sizes (13.4 ± 1.4 nm, 36.6 ± 2.6 nm, and 68.6 ± 3.8 nm) with over 80% of encapsulation efficiency and sustained drug release. Among them, the small-sized ST-d-rHDL showed the strongest cholesterol efflux capacity and inhibitory effect on intracellular lipid deposition in foam cells. In addition, the results showed that the loaded drug did not compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL. CONCLUSION: Compared to the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced cellular cholesterol efflux capacity similar to drug-free one, and the effect of particle size on cholesterol efflux was not influenced by the drug loading.

A green-inspired method to prepare non-split high-density lipoprotein (HDL) carrier with anti-dysfunctional activities superior to reconstituted HDL.

Numerous studies have demonstrated that dysfunctional high-density lipoprotein (HDL), especially oxidized HDL (OxHDL), could generate multifaceted in vivo proatherogenic effects that run counter to the antiatherogenic activities of HDL. It thereby reminded us that the in vitro reconstituted HDL (rHDL) might encountered with oxidation-induced dysfunction. Accordingly, a green-inspired method was employed to recycle non-split HDL from human plasma fraction IV. Then it was compared with rHDL formulated by an ethanol-injection method in terms of physicochemical properties and anti-dysfunctional activities. Results exhibited that rHDL oxidation extent exceeded that of non-split HDL evidenced by higher malondialdehy content, weaker inhibition on low-density lipoprotein (LDL) oxidation and more superoxide anion. The reserved paraoxonase-1 activity on non-split HDL could partially explain for above experimental results. In the targeted transport mechanism experiment, upon SR-BI receptor inhibition and/or CD36 receptor blockage, the almost unchanged non-split HDL uptake in lipid-laden macrophage indicated its negligible oxidation modification profile with regard to rHDL again. Furthermore, compared to rHDL, better macrophage biofunctions were observed for non-split HDL as illustrated by accelerated cholesterol efflux, inhibited oxidized LDL uptake and lessened cellular lipid accumulation. Along with decreased ROS secretion, obviously weakened oxidative stress damage was also detected under treatment with non-split HDL. More importantly, foam cells with non-split HDL-intervention inspired an enhanced inflammation repression and apoptosis inhibition effect. Collectively, the anti-dysfunctional activities of non-split HDL make it suitable as a potential nanocarrier platform for cardiovascular drug payload and delivery.

Iron-bound organic carbon dynamics in peatland profiles: The preservation equivalence of deep and surface soil.

More than half of the carbon pools in peatlands are stored in the soil layers below 30 cm, yet little is known about the carbon stabilizing factors at these depths. Although iron oxide minerals are considered to be important for stabilizing organic carbon (OC), their role in the preservation of OC in peatlands, especially in the deep layers, is poorly understood. Here, we collected 1 m soil profiles from six peatlands in Central and West China to quantitatively study the vertical distribution characteristics of iron-bound OC (Fe-bound OC), and the influencing physicochemical properties of the soil. The results showed that the content of reactive iron (FeR) was enriched in the top layer and decreased gradually with depth. While Fe-bound OC was positively correlated with FeR, its concentration did not decrease with depth in the peat profile. There were no obvious trends in the distributions of FeR and Fe-bound OC with water level fluctuations in the peat profile. In addition, the proportion of Fe-bound OC to soil organic carbon in the deep peat (31 to 100 cm) was equivalent to that in the surface peat (0 to 30 cm), indicating that iron oxide mineral provides comparable protection of OC in both layers. According to upper estimates of global peatland carbon storage (612 Pg), it could be predicted that 23.81 ± 11.75 Pg of OC is protected by association with FeR. These results indicated that iron oxide minerals are the effective "rusty sink" of OC sequestration in peatland, and a key factor for its long-term preservation. The results from this study make a valuable contribution to the carbon dynamics knowledgebase for peatlands, and provide a basis for improved predictive simulations.

Cyclodextrin boostered-high density lipoprotein for antiatherosclerosis by regulating cholesterol efflux and efferocytosis.

A promising therapy for atherosclerosis treatment was designed by targeting LXR receptor (LXR) on atherosclerotic macrophage, where LXR activation could regulate cholesterol efflux and efferocytosis. Herein, a sequential-targeting nanoplatform (HT-rHDL) was constructed to deliver LXR agonist into macrophage, which was composed of discoidal reconstituted high-density lipoprotein (d-rHDL) core for agonist encapsulation and external modifications: (i) the outermost hyaluronan, targeting injured endothelium; (ii) modified ß-cyclodextrin of d-rHDL, accelerating cholesterol efflux of foam cells; (iii) conjugated apolipoprotein A-I of d-rHDL, targeting macrophage. This design underlines that the nanoplatform could increase its plaque accumulation, accomplish cholesterol efflux-remodeling-drug delivery behavior and specifically activate LXR in macrophage. After a 3-month treatment with HT-rHDL, 31.47% plaque area reduction, 56.0% lipid accumulation decrease, obvious inflammation resolution and enhanced plaque stability were observed. Furthermore, the atherosclerosis intervention was demonstrated to benefit from the upregulations of ABC transporters and Mer tyrosine kinase. Collectively, HT-rHDL provides new strategies to regress atherosclerosis.

Homogeneous selection is stronger for fungi in deeper peat than in shallow peat in the low-temperature fens of China.

Peatlands have accumulated enormous amounts of carbon over millennia, and climate changes threatens the release of this carbon into the atmosphere. Fungi are crucial drivers of global carbon cycling because they are the principal decomposer of organic matter in peatlands. However, the fungal community composition and ecological preferences in peat remain unclear, which restricts our ability to evaluate the role of the fungal community in peat biogeochemical functions. We investigated 54 soils from 6 low-temperature peatlands across China to fill this knowledge gap. The peat was divided into above-water table (AWT) and below-water table (BWT) layers based on the water table fluctuation. We investigated fungal community assembly processes and drivers for each peat layer. The results showed that fungal communities differed significantly among peat layers. The relative abundance of symbiotrophs was significantly higher in the AWT (17.4%) than in the BWT (9.0%), while the abundances of yeast and litter saprotrophs were obviously lower in the AWT than in the BWT. Our results revealed that the assemblage of both fungal taxonomic and phylogenetic communities was mainly governed by stochastic processes in both AWT (87.8%) and BWT (58.6%) layers. However, in the BWT, the relative importance of deterministic processes (28.4%) significantly increased, indicating a potential deterministic environmental selection induced by permanently anaerobic condition. Mean annual precipitation and mean annual temperature were the most critical drives for the assemblage of the fungal community in the BWT. These observations collectively indicate that fungal community assembly is depth-dependent, implying different community assembly mechanisms and ecological functions along the peat profile. These findings highlight the importance of climate driven deep peat fungal community composition assemblages and suggest the potential to project the changes in fungal diversity with ongoing climate change.

Forecasting Carbon Price in China: A Multimodel Comparison.

With the global concern for carbon dioxide, the carbon emission trading market is becoming more and more important. An accurate forecast of carbon price plays a significant role in understanding the dynamics of the carbon trading market and achieving national emission reduction targets. Carbon prices are influenced by many factors, which makes carbon price forecasting a complicated problem. In recent years, deep learning models are widely used in price forecasting, because they have high forecasting accuracy when dealing with nonlinear time series data. In this paper, Multivariate Long Short-Term Memory (LSTM) in deep learning is used to forecast carbon prices in China, which takes into account the factors affecting the carbon price. The historical time series data of carbon prices in Hubei (HBEA) and Guangdong (GDEA) and three traditional energy prices affecting carbon prices from 5 May 2014 to 22 July 2021 are collected to form two data sets. To prove the forecast effect of our model, this paper not only uses Multivariate LSTM, Multilayer Perceptron (MLP), Support Vector Regression (SVR), and Recurrent Neural Network (RNN) to forecast the same data, but also compares the forecast results of Multivariate LSTM with the existing research on HBEA and GDEA forecast based on deep learning recently. The results show that the MAE, MSE, and RMSE obtained by the Multivariate LSTM are all smaller than other prediction models, which proves that the model is more suitable for carbon price forecast and offers a new approach to carbon prices forecast. This research conclusion also provides some policy implications.

Correction: Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization.

Correction for 'Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization' by Qiqi Zhang et al., Biomater. Sci., 2021, 9, 6153-6168, DOI: 10.1039/D1BM00610J.

Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization.

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into the anti-inflammatory phenotype (M2) for atherosclerosis regression. These might be realized simultaneously by drug-loaded discoidal reconstituted high-density lipoproteins (d-rHDLs) with the functions of cellular cholesterol efflux and targeted drug delivery on macrophages. However, cholesterol reception can drive the remodelling of d-rHDLs, which serves to release drugs specifically in the atherosclerotic plaque but might incur premature drug leakage in blood circulation. Given that, the proposed strategy is to inhibit the remodelling behaviour of the carrier in blood circulation and responsively accelerate it under the atherosclerotic microenvironmental stimulus. Herein, atorvastatin calcium-loaded d-rHDL was modified by a PEGylated ferrocene/ß-cyclodextrin supramolecular copolymer (PF/TC) to construct ROS-responsive PF/TC-AT-d-rHDL, which is expected to possess plasma stability and biosafety as well as triggered drug release by cholesterol efflux promotion. As a result, PF/TC-AT-d-rHDL could responsively dissemble into ß-cyclodextrin modified AT-d-rHDL under the ROS-triggered dissociation of PF/TC, therefore exhibiting increased cholesterol efflux from the cholesterol donor and drug release through the remodelling behaviour of the carrier in vitro. Moreover, PF/TC-AT-d-rHDL enhanced cellular cholesterol removal in foam cells after response to ROS, inhibiting intracellular lipid deposition compared with other d-rHDL carriers. Interestingly, cellular drug uptake was significantly promoted upon cellular cholesterol removal by restoring the permeability and fluidity of foam cell membranes as indicated by flow cytometry and fluorescence polarization analysis, respectively. Importantly, compared with untreated foam cells, PF/TC-AT-d-rHDL obviously increased the ratio of M2/M1 by 6.3-fold, which was even higher than the effect of PF/TC-d-rHDL (3.4-fold) and free drugs (1.9-fold), revealing that PF/TC-AT-d-rHDL synergistically promoted the M2 polarization of macrophages. Accordingly, PF/TC-AT-d-rHDL boosted the secretion of anti-inflammatory cytokines and inhibited that of inflammatory cytokines. Collectively, PF/TC-AT-d-rHDL exerted synergistic M2 polarization effects on foam cells for atherosclerotic immunomodulatory therapy via responsively mediating cholesterol efflux and delivering drugs.

A chromodomain protein mediates heterochromatin-directed piRNA expression.

PIWI-interacting RNAs (piRNAs) play significant roles in suppressing transposons, maintaining genome integrity, and defending against viral infections. How piRNA source loci are efficiently transcribed is poorly understood. Here, we show that in Caenorhabditis elegans, transcription of piRNA clusters depends on the chromatin microenvironment and a chromodomain-containing protein, UAD-2. piRNA clusters form distinct focus in germline nuclei. We conducted a forward genetic screening and identified UAD-2 that is required for piRNA focus formation. In the absence of histone 3 lysine 27 methylation or proper chromatin-remodeling status, UAD-2 is depleted from the piRNA focus. UAD-2 recruits the upstream sequence transcription complex (USTC), which binds the Ruby motif to piRNA promoters and promotes piRNA generation. Vice versa, the USTC complex is required for UAD-2 to associate with the piRNA focus. Thus, transcription of heterochromatic small RNA source loci relies on coordinated recruitment of both the readers of histone marks and the core transcriptional machinery to DNA.

CDE-1 suppresses the production of risiRNA by coupling polyuridylation and degradation of rRNA.

BACKGROUND: Modification of RNAs, particularly at the terminals, is critical for various essential cell processes; for example, uridylation is implicated in tumorigenesis, proliferation, stem cell maintenance, and immune defense against viruses and retrotransposons. Ribosomal RNAs can be regulated by antisense ribosomal siRNAs (risiRNAs), which downregulate pre-rRNAs through the nuclear RNAi pathway in Caenorhabditis elegans. However, the biogenesis and regulation of risiRNAs remain obscure. Previously, we showed that 26S rRNAs are uridylated at the 3'-ends by an unknown terminal polyuridylation polymerase before the rRNAs are degraded by a 3' to 5' exoribonuclease SUSI-1(ceDIS3L2). RESULTS: Here, we found that CDE-1, one of the three C.elegans polyuridylation polymerases (PUPs), is specifically involved in suppressing risiRNA production. CDE-1 localizes to perinuclear granules in the germline and uridylates Argonaute-associated 22G-RNAs, 26S, and 5.8S rRNAs at the 3'-ends. Immunoprecipitation followed by mass spectrometry (IP-MS) revealed that CDE-1 interacts with SUSI-1(ceDIS3L2). Consistent with these results, both CDE-1 and SUSI-1(ceDIS3L2) are required for the inheritance of RNAi. CONCLUSIONS: This work identified a rRNA surveillance machinery of rRNAs that couples terminal polyuridylation and degradation.