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Science Papers on Crystal Structure of Bacteriophages, Silencing of ALS-Linked Gene

The crystal structures of multiple metagenome-derived single-stranded RNA (ssRNA) bacteriophages are published in Science Advances this week, providing new insights into this group of small bacterial viruses. Metagenomic sequencing efforts have uncovered an immense number of distinct uncultured ssRNA phages, yet little is known about the structure, host bacteria, lysis strategies, and other essential characteristics of these newly discovered life forms. To address this knowledge gap, scientists from the Latvian Biomedical Research and Study Center recombinantly expressed metagenome-derived ssRNA phage coat proteins (CPs) to produce virus-like particles and determined the three-dimensional structure of 22 previously uncharacterized ssRNA phage capsids covering nine distinct CP types. They find substantial deviations from the previously known ssRNA phage CP fold, uncover an unusual prolate particle shape, and reveal a previously unseen dsRNA binding mode. 

Gene-silencing antisense oligonucleotides (ASOs) targeting a gene involved in many cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) may help reduce the pathogenic accumulation of a protein that is a hallmark of the two neurodegenerative disorders. G4C2 repeat expansions in the C9orf72 gene are the most common causes of ALS and FTD, which frequently feature the buildup of TAR DNA-binding protein 43 (TDP-43) in the brains of patients. As reported in Science Translational Medicine this week, a Mayo Clinic-led team found that a poly glycine-arginine protein [poly(GR)] produced by the C9orf72 repeat expansion enhanced the formation of TDP-43 in vitro and in mice by altering nucleocytoplasmic transport. Treating the mice with poly(GR)-targeting ASOs, meanwhile, reduced aggregation of TDP-43 aggregation and protected neurons from damage. In addition to establishing a mechanistic link between the C9orf72 repeat expansion and TDP-43 proteinopathy, the study highlights the potential of G4C2-targeting drugs.

The Scan

Genetic Ancestry of South America's Indigenous Mapuche Traced

Researchers in Current Biology analyzed genome-wide data from more than five dozen Mapuche individuals to better understand their genetic history.

Study Finds Variants Linked to Diverticular Disease, Presents Polygenic Score

A new study in Cell Genomics reports on more than 150 genetic variants associated with risk of diverticular disease.

Mild, Severe Psoriasis Marked by Different Molecular Features, Spatial Transcriptomic Analysis Finds

A spatial transcriptomics paper in Science Immunology finds differences in cell and signaling pathway activity between mild and severe psoriasis.

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.