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PNAS Papers on Codon Usage Effects on Transcription, Endotoxic Shock LncRNA, More

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.

Investigators in the US and China consider codon usage consequences on transcription in the Neurospora fungus. With the help of an RNA sequencing-based genetic screens in wild-type and knock-out strains of Neurospora — along with chromatin immunoprecipitation sequencing and other approaches — the team saw ties between gene codon usage bias across the genome and levels of nuclear RNA in the filamentous fungus model, narrowing in on 18 genes that code for transcription factors, chromatin regulators, and other factors suspected of contributing to codon usage effects on gene expression. "Most of these factors, such as the H3K36 methyltransferase, are chromatin regulators or transcription factors," the authors report. "Together, our results suggest that the transcriptional effect of codon usage is mediated by multiple transcriptional regulatory mechanisms."

A team from the University of California, Santa Cruz, and the University of Texas Southwestern Medical Center describe a long non-coding RNA (lncRNA) involved in innate immunity and endotoxic shock response for a paper scheduled to appear in PNAS this week. Using RNA-seq, the researchers focused in on a lncRNA that they call "gastric adenocarcinoma predictive long intergenic non-coding RNA," or GAPLINC through a series of RNA sequencing analyses on human or mouse macrophage cells derived from monocyte immune cells. Their results suggest that GAPLINC levels are enhanced over the process of macrophage differentiation, but drop in response to inflammatory activation, while mice missing GAPLINC appear resistant to endotoxic shock prompted by bacterial lipopolysaccharide endotoxins. The authors say these and other results "identify a previously unknown function for GAPLINC as a negative regulator of inflammation and uncover a key role for this lncRNA in modulating endotoxic shock."

University of California, San Francisco, researchers report on a role for the autoimmune disease-related, conserved transmembrane protein-coding gene TMEM39A in lysosome organelle functions in the model organism Caenorhabditis elegans. The team used CRISPR-Cas9 gene editing experiments, fluorescence imaging, protein interaction assays, and other methods to dig into TMEM39A function following a prior genome-wide RNA interference screen that implicated the gene in cell stress response. Results from the authors' C. elegans and mammalian cell experiments suggest that TMEM39A helps to regulate the position of lysosomes and related pathway signaling through its interactions with dynein protein components. "As lysosomes are implicated in various aspects of immune system dysfunction, including abnormal cytokine secretion and antigen presentation, our study provides an important mechanistic insight suggesting how TMEM39A might contribute to autoimmunity like multiple sclerosis and lupus."

The Scan

Guidelines for Ancient DNA Work

More than two dozen researchers have developed new ethical guidelines for conducting ancient DNA research, which they present in Nature.

And Cleared

A UK regulator has cleared former UK Prime Minister David Cameron in concerns he should have registered as a consultant-lobbyist for his work with Illumina, according to the Financial Times.

Suit Over Allegations

The Boston Globe reports that David Sabatini, who was placed on leave from MIT after allegations of sexual harassment, is suing his accuser, the Whitehead Institute, and the institute's director.

Nature Papers on Esophageal Cancer, Origin of Modern Horses, Exome Sequencing of UK Biobank Participants

In Nature this week: genetic and environmental influences of esophageal cancer, domestic horse origin traced to Western Eurasian steppes, and more.