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PNAS Papers on Transcriptional Effects of Mutagens, Heart Rhythm Regulator, Antibiotic Resistance

Investigators at the University of Pennsylvania, the University of Southern California, and elsewhere document transcriptional glitches in Saccharomyces cerevisiae budding yeast cells exposed to mutagenic compounds such as an alkylating agent. Using massively parallel, high-fidelity RNA sequencing, transcriptional kinetic experiments, and other approaches, the team identified new genetic mutations in the model organism after exposure to the mutagen, along with a host of previously unappreciated transcription errors in actively dividing and nondividing cells. "[W]e demonstrate that mutagens can lower the fidelity of transcription in yeast, worms, flies, and mice by promoting the misincorporation of nucleotides by RNA polymerases," the authors report. "These observations establish a mechanism by which the environment, our lifestyle choices, and work-related exposures may promote the age of onset, severity, and progression of various diseases."

A University of Ottawa-led team outlines a role for the transcription factor-coding gene GATA6 in regulating the development of the heart's main pacemaker, known as the sinus node, as well as heart rhythm in a mouse model missing one copy of the gene. Based on a series of electrocardiogram, protein interaction, protein localization, and other experiments on mice with GATA6 haploinsufficiency, the researchers suggest that GATA6 "may be a genetic modifier of cardiac conduction disease, including sick sinus syndrome." The researchers add that "[t]he data identify GATA6 as an important regulator of the [sinus node] and provide a molecular basis for understanding the conduction abnormalities associated with GATA6 mutations in humans" and that "GATA6 may be a potential modifier of the cardiac pacemaker."

Researchers from Genentech describe copy number heterogeneity behind resistance to the antibiotic arylomycin in two bacterial species profiled by single-molecule nanopore sequencing. With the help of MinION ultra-long read nanopore sequencing, the team tracked copy number heterogeneity in Escherichia coli and Acinetobacter baumannii clonal populations grown from individual cells selected for resistance to the drug, including variable and unstable amplifications affecting a lepB gene that codes for a signal peptidase enzyme targeted by arylomycin antibiotics. "[T]his remarkable heterogeneity, and the evolutionary plasticity it fuels, illustrates how gene amplification can enable bacterial populations to respond rapidly to novel antibiotics," the authors say, noting that their work "establishes a rationale for further nanopore sequencing studies of heterogeneous cell populations to uncover [copy number] variability at single-molecule resolution."

The Scan

More Boosters for US

Following US Food and Drug Administration authorization, the Centers for Disease Control and Prevention has endorsed booster doses of the Moderna and Johnson & Johnson SARS-CoV-2 vaccines, the Washington Post writes.

From a Pig

A genetically modified pig kidney was transplanted into a human without triggering an immune response, Reuters reports.

For Privacy's Sake

Wired reports that more US states are passing genetic privacy laws.

Science Paper on How Poaching Drove Evolution in African Elephants

In Science this week: poaching has led to the rapid evolution of tuskless African elephants.