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Science Reports on Approach to Detect Multiple RNA Biomarkers, Studies of Bacteriophages' Z Genomes

A diagnostic platform that can detect multiple RNA biomarkers in a single test using noncanonical CRISPR RNAs (crRNAs) is described in Science this week. In the report, a team led by scientists from the Helmholtz-Center for Infection Research finds that crRNAs, which are used in CRISPR-Cas9 systems to target foreign genetic material for degradation, can be derived from cellular RNAs not associated with viral defense in type II CRISPR systems. Based on this, the investigators engineered crRNAs that link the presence of an RNA of interest to DNA targeting with different Cas9 orthologs, forming the basis for their multiplexable diagnostic platform. They demonstrate the platform by detecting RNAs from multiple viruses in a single test, as well as distinguishing SARS-CoV-2 from one of its variants with single-base resolution in patient samples.

Three studies appearing in Science this week provide new details about the Z-genome of bacteriophages. Genomic DNA is composed of four standard nucleotides, each with a different nucleobase — adenine (A), thymine (T), cytosine (C), and guanine (G) — that is conserved across all domains of life. However, around 40 years ago, the DNA virus cyanophage S-2L was discovered with all instances of A substituted with 2-aminoadenine (Z) throughout its genome. In two of the papers, independent teams from Tianjin University and Institut Pasteur characterize the proteins involved in the biosynthesis of Z, while in the third paper a group led by investigators from Université Paris-Saclay identify a Z-specific polymerase that is responsible for assembling Z-substituted DNA from available nucleotides. In an accompanying perspective, a pair of Yale University researchers discuss the implications of the findings and how they may help drive new innovations in materials and biotechnology.

The Scan

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.

Using Bees to Gain Insights into Urban Microbiomes

As bees buzz around, they pick up debris that provides insight into the metagenome of their surroundings, researchers report in Environmental Microbiome.

Age, Genetic Risk Tied to Blood Lipid Changes in New Study

A study appearing in JAMA Network Open suggests strategies to address high lipid levels should focus on individuals with high genetic risk and at specific ages.

Study Examines Insights Gained by Adjunct Trio RNA Sequencing in Complex Pediatric Disease Cases

Researchers in AJHG explore the diagnostic utility of adding parent-child RNA-seq to genome sequencing in dozens of families with complex, undiagnosed genetic disease.