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Cell Papers Explore Translation, Messenger RNA Localization

An international team led by investigators in Germany tracks messenger RNA expression and translation in 80 human hearts. Using RNA sequencing, Ribo-seq, totRNA-seq, proteomics, and other approaches, the researchers profiled mRNA levels, ribosomal footprints, circular RNAs, proteins, microproteins, and more in left ventricular cardiac tissue samples from 65 individuals with dilated cardiomyopathy and 15 without, following up on their human heart results in cell line and mouse models. Along with previously unappreciated transcription and translation products, regulatory insights, and new dilated cardiomyopathy clues, the authors saw "extensive translational control of cardiac gene expression … orchestrated in a process-specific manner."

Researchers from the Netherlands and US describe a real-time, mRNA translation visualization approach called MoonTag, which relies on genetically encoded fluorescence labeling involving specific intracellular antibodies and peptide array epitopes. By applying MoonTag in combination with a related "SunTag" method, developed to label nascent polypeptides in past studies, the team identified heterogeneous translation patterns in human cell lines, including stochastic start site selection and variable ribosome interactions for a given gene. "By placing MoonTag and SunTag sequences in different translation reading frames, each driven by distinct translation start sites, start site selection of individual ribosomes can be visualized in real time" the authors say, adding that the broader strategy "provides key insights into translation start site selection heterogeneity and provides a powerful toolbox to visualize complex translation dynamics.

Finally, a Stanford University- and Chan Zuckerberg Biohub team presents an RNA localization atlas established with an RNA proximity labeling-based method known as APEX-seq. The team used the approach, which relies on the APEX2 peroxidase enzyme, to map some 3,250 gene transcripts within nine subcellular locations within human cells. In general, nuclear transcripts had a radial organization at the inner nuclear pore, for example, while two pathways led to mitochondrial localization. More broadly, the authors report, "[o]ur data reveal correlations between localization of mRNAs and the protein products they encode, as well as patterns of RNA localization and underlying genome architecture."