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Study Points to Synonymous Mutation Effects on E. Coli Enzyme Activity

A team from Pennsylvania State University and Johns Hopkins University points to potential structural and functional consequences of synonymous mutations that alter the RNA sequence of a gene without changing the amino acid composition of the resulting protein. As they report in Nature Chemistry, the investigators tracked synonymous mutations' consequences in Escherichia coli genes coding for the type III chloramphenicol acetyltransferase, D-alanine-D-alanine ligase B, and dihydrofolate reductase enzymes, uncovering activity shifts in enzymes with synonymous mutations using multiscale modeling that took protein synthesis speed, post-translational patterns, robustness, and mechanical features into account. Along with apparent shifts in translation elongation speed, the authors point to other potential synonymous mutation effects, including possible protein misfolding. "Synonymous mutations alter translation elongation speeds and change the population of nascent chain conformations in entangled states that are near native but have lower catalytic efficiencies than that of the native state," the authors report, noting that "the specific activity — a quantity averaged over the populations of proteins in different conformational states — can increase or decrease due to synonymous mutations."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.