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Analyses of 2024 daily mortality data from 654 regions in 32 European countries identified 62,775 heat-related deaths and informed a real-time early warning model that predicts heat-related health emergencies at least 1 week in advance.

CPEB1 is known to regulate cytoplasmic polyadenylation, and is now shown to have a second function in the nucleus; it associates with the cleavage and polyadenylation machinery, thereby promoting usage of an upstream poly(A) signal in many messenger RNAs, and affecting alternative splicing.

Clarke et al. identify chromatin factor ZNF280A, which is recruited to damaged chromatin where it promotes long-range DNA-end resection. Loss of ZNF280A is linked to genome instability in patients with 22q11.2 distal deletion syndrome.

The molecular mechanisms of how small changes in the degree of inclusion of a neuron-specific microexon in CPEB4 lead to dominant-negative effects in the expression of genes associated with autism spectrum disorder are identified.

mRNA translational control by CPEBs is reactivated in cancer. Here, the authors show that the insertion of CPE regulatory sequences in the 3′ UTR of the E1A viral gene induces oncoselectivity, with oncolytic potency in cancer cells but attenuated toxicity in normal tissues.

New data reveal how Musashi binding to Xenopus oocyte mRNAs promotes changes in RNA secondary structure that modulate CPEB1 binding and influence polyadenylation and translational efficiency.

Cytoplasmic polyadenylation-driven translational control is known to regulate the expression of stored maternal mRNA in meiosis and early embryonic divisions. CPEB proteins mediate cell cycle phase-specific changes in polyadenylation that are also required for cell proliferation and mitotic entry in other actively dividing cells.

CPEB4 binds the mRNA of genes known to be associated with autism and shows an isoform imbalance in individuals with autism, and an equivalent imbalance in mice induces an autism-like phenotype.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

A genome-wide screen for mRNAs that were polyadenylated at meiotic transitions noted that many contained an ARE, a deadenylation element, as well as a cytoplasmic polyadenylation element (CPE). One such mRNA encodes C3H-4, a protein that promotes shortening of polyA tails. The data suggest a model in which the early extension of polyadenylation through the CPE element leads to expression of C3H-4, which then acts in a negative feedback loop to deadenylate, and deactivate, those mRNAs that also contain an ARE, thereby allowing exit from metaphase.

Cytoplasmic polyadenylated transcripts have been poorly characterized, particularly in cancer. Here the authors identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma and show that it controls melanoma drivers MITF and RAB27A.

This ecological analysis using the Eurostat database estimated that summer 2022, the hottest summer on record, was associated with over 61,000 heat-related deaths across 35 countries in Europe, with the highest mortality rates in countries near the Mediterranean Sea.

This report uncovers a role for the mRNA binding factor CPEB4 in cancer. CEPB4 is upregulated in human pancreatic adenocarcinomas and glioblastomas, where it supports tumor growth by providing translational activation of normally silent mRNAs, including tPA, an important contributor to malignancy. The findings illustrate that altered post-transcriptional regulation of gene expression may be an important contributing factor to cancer.

Predictions suggest that a high proportion of plant species will be threatened with extinction in the near future. A global assessment of the threat status of cacti suggests that these iconic plants are amongst the most threatened taxonomic groups, with 31% of the 1,478 evaluated species at risk of extinction.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Pancreatic acinar differentiation can be tumour suppressive for pancreatic ductal adenocarcinoma (PDAC). Here the authors identify nuclear factor I family of transcription factors NFIC as a regulator of pancreatic acinar cell function that restrains mutant KRas-driven pancreas cancer initiation in mice.

Maillo et al. show that in hepatocytes ER stress upregulates CPEB4 through the UPR and circadian clock, leading to CPEB4-mediated translation for mitochondrial and ER homeostasis. CPEB4 loss leads to ageing- and high fat diet-induced liver steatosis.

How daylight saving time shift (DST) affects mortality dynamics on a large population scale remains unknown. Here, the authors examine the impact of DST on all-cause mortality in 16 European countries for the period 1998-2012.

European population exposure to most air pollutants has been reduced significantly, however for PM2.5 and O3, single pollutant and compound events remain a threat, particularly in Southern and Eastern Europe

Analyses of the year 2023, the warmest on record globally, estimated 47,690 heat-related deaths across 35 countries in Europe, which would have been 80% higher in the absence of any societal adaptations.

Blood brain barrier (BBB) opening is being investigated as a therapeutic approach for neurodegenerative diseases. Here, the authors report the results of a phase I trial to evaluate the feasibility and safety of BBB opening of the right parieto-occipito-temporal cortex in Parkinson´s disease with dementia.

Malumbres and colleagues reveal that mitotic arrest is accompanied by reduced mitochondrial mass and oxidative respiration resulting in activation of AMPK and induction of glycolysis to promote cell survival.

Genome-wide association studies (GWAS) have revealed gene variants associated with breast cancer, but their association with breast cancer development in Latinas is not clear. Here, the authors carry out a GWAS of breast cancer in Latinas and identify a significant protective variant of Indigenous American origin in the 6q25 region.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Recent studies have revealed how poly(A) tail length and the selection of alternative polyadenylation sites contribute to translational control. This Review discusses how mechanisms of alternative polyadenylation, deadenylation and cytoplasmic polyadenylation are coordinated to modulate gene expression in inflammation, learning and memory acquisition, and early development.

Yazdani et al. identify gene signatures by integrating transcriptomic-causal networks into overall survival analysis, providing interpretable biomarkers for patient stratification. Gene signatures are found in metastatic colorectal cancer that indicate patients with specific profiles might benefit from cetuximab or bevacizumab.

An in vitro mass cytometry study focusing on age and adjuvant-specific activation of human blood mononuclear cells reveals NK cells as the key source of TLR7/8 agonist induced innate IFNγ responses.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.