CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex

The exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout cell lines to elucidate the cellular role of CASC3. In the knockout cells, overall EJC composition and EJC-dependent splicing are unchanged. A transcriptome-wide analysis reveals that hundreds of mRNA isoforms targeted by nonsense-mediated decay (NMD) are upregulated. Mechanistically, recruiting CASC3 to reporter mRNAs by direct tethering or via binding to the EJC stimulates mRNA decay and endonucleolytic cleavage at the termination codon. Building on existing EJC-NMD models, we propose that CASC3 equips the EJC with the persisting ability to communicate with the NMD machinery in the cytoplasm. Collectively, our results characterize CASC3 as a peripheral EJC protein that tailors the transcriptome by promoting the degradation of EJC-dependent NMD substrates

Interactions between arbuscular mycorrhizal fungi and intraspecific competition affect size and size inequality of Plantago lanceolata L.

Intraspecific competition causes decreases in plant size and increases in size inequality. Arbuscular mycorrhizas usually increase the size and inequality of non-competing plants, but mycorrhizal effects often disappear when plants begin competing. We hypothesized that mycorrhizal effects on size inequality would be determined by the experimental conditions, and conducted simultaneous field and glasshouse experiments to investigate how AM fungi and intraspecific competition determine size inequality in Plantago lanceolata. 2 As predicted, plant size was reduced when plants were competing, in both field and controlled conditions. However, size inequality was unexpectedly reduced by competition. Plants may have competed in a symmetric fashion, probably for nutrients, rather than the more common situation, in which plant competition is strongly asymmetric. 3 Mycorrhizas had no effect on plant size or size inequality in competing plants in either field or controlled conditions, possibly because competition for nutrients was intense and negated any benefit the fungi could provide. 4 The effects of mycorrhizas on non-competing plants were also unexpected. In field-grown plants, AM fungi increased plant size, but decreased size inequality: mycorrhizal plants were more even in size, with few very small individuals. In glasshouse conditions, mycorrhizal colonization was extremely high, and was generally antagonistic, causing a reduction in plant size. Here, however, mycorrhizas caused an increase in size inequality, supporting our original hypothesis. This was because most plants were heavily colonized and small, but a few had low levels of colonization and grew relatively large. 5 This study has important implications for understanding the forces that structure plant communities. AM fungi can have a variety of effects on size inequality and thus potentially important influences on long-term plant population dynamics, by affecting the genetic contribution of individuals to the next generation. However, these effects differ, depending on whether plants are competing or not, the degree of mycorrhizal colonization and the responsiveness of the plant to different colonization densities

A human biomonitoring (HBM) Global Registry Framework: Further advancement of HBM research following the FAIR principles.

Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF

Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associ