Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
In a paper scheduled to appear in PNAS this week, a National Institute of Allergy and Infectious Disease-led team shares findings pointing to a role for the host receptor transporter protein 4 (RTP4) gene in severe malaria or viral infections in mice. The researchers relied on a "trans-species expression quantitative trait locus," or Ts-eQTL, screening approach and array-based gene expression profiling on spleen samples from mice exposed to the Plasmodium yoelii parasite, focusing in on the RTP4 gene for follow-up functional experiments in cell lines and in mice exposed to another malaria parasite, P. berghei, or to the West Nile virus. Together, the results hint that RTP4 interacts with and negatively regulates the type I interferon immune pathways, while mice missing the gene appeared to have more pronounced antimalaria and antiviral responses.
Researchers from the University of Wisconsin at Madison take a look at replication in positive-strand RNA viruses using the nodavirus flock house virus (FHV) model. Using optimized cryoelectron microscopy and other approaches, the team got a clearer look at the nodavirus RNA replication complex crown, identifying a dozen crown segments and three broader sub-domains that may inform future studies of replication structures and functions in still other positive-strand RNA viruses. "Positive-strand RNA viruses constitute the largest genetic class of viruses and include many high-impact pathogens, such as SARS-CoV-2 (COVID-19 pandemic coronavirus), MERS CoV, Zika, chikungunya, dengue, and hepatitis C viruses," the authors write, noting that "urgent needs exist to define RNA replication complex structure and function at a molecular level."
A team from the University of Texas at Austin and the US Department of Energy's Joint Genome Institute outline a CRISPR-modified Cas9 gene editing-based approach for tinkering with gene expression in the Saccharomyces cerevisiae yeast model organism. The bidirectional gene expression titration strategy involves a plasmid library, CRISPR-dCas9 gene editing, and next-generation sequencing, the researchers explain. When they applied this approach to nearly 1,000 yeast metabolic network genes, for example, the authors tracked down genes that appear to be essential in S. cerevisiae yeast genes grown using alternative sugar sources or in yeast models producing betaxanthin pigments. "Taken together," they write, "these two case studies highlight the importance of utilizing bidirectional titration of gene expression for identification of novel gene targets as well as their optimal level of expression."