rG4detector, a novel RNA G-quadruplex predictor, uncovers their impact on stress granule formation.

RNA G-quadruplexes (rG4s) are RNA secondary structures, which are formed by guanine-rich sequences and have important cellular functions. Existing computational tools for rG4 prediction rely on specific sequence features and/or were trained on small datasets, without considering rG4 stability information, and are therefore sub-optimal. Here, we developed rG4detector, a convolutional neural network to identify potential rG4s in transcriptomics data. rG4detector outperforms existing methods in both predicting rG4 stability and in detecting rG4-forming sequences. To demonstrate the biological-relevance of rG4detector, we employed it to study RNAs that are bound by the RNA-binding protein G3BP1. G3BP1 is central to the induction of stress granules (SGs), which are cytoplasmic biomolecular condensates that form in response to a variety of cellular stresses. Unexpectedly, rG4detector revealed a dynamic enrichment of rG4s bound by G3BP1 in response to cellular stress. In addition, we experimentally characterized G3BP1 cross-talk with rG4s, demonstrating that G3BP1 is a bona fide rG4-binding protein and that endogenous rG4s are enriched within SGs. Furthermore, we found that reduced rG4 availability impairs SG formation. Hence, we conclude that rG4s play a direct role in SG biology via their interactions with RNA-binding proteins and that rG4detector is a novel useful tool for rG4 transcriptomics data analyses.

Physically interacting beta-delta pairs in the regenerating pancreas revealed by single-cell sequencing.

OBJECTIVES: Until recently, communication between neighboring cells in islets of Langerhans was overlooked by genomic technologies, which require rigorous tissue dissociation into single cells. METHODS: We utilize sorting of physically interacting cells (PICs) with single-cell RNA-sequencing to systematically map cellular interactions in the endocrine pancreas after pancreatectomy. RESULTS: The pancreas cellular landscape features pancreatectomy associated heterogeneity of beta-cells, including an interaction-specific program between paired beta and delta-cells. CONCLUSIONS: Our analysis suggests that the particular cluster of beta-cells that pairs with delta-cells benefits from stress protection, implying that the interaction between beta- and delta-cells might safeguard against pancreatectomy associated challenges. The work encourages testing the potential relevance of physically-interacting beta-delta-cells also in diabetes mellitus.

microRNAs trip down memory lane.

A new study by Islam et al, in this issue of EMBO Molecular Medicine, reports three microRNAs in the blood that are linked to inter-individual differences in cognition, prior to any sign of cognitive decline. The novel miRNA biomarkers may assist in predicting the risk of cognitive decline and later of developing dementia and can contribute to decision strategies about early therapeutic interventions.