Stem-loop binding protein and metal carcinogenesis.

Pre-mRNA processing of the replication-dependent canonical histone mRNAs requires an endonucleolytic cleavage immediately after a conserved stem loop structure which occurs before RNA Pol II encounters any poly(A) signal. Thus, in contrast to all other eukaryotic mRNAs, the canonical histone mRNAs are not polyadenylated in their 3' ends. The binding of stem-loop binding protein (SLBP) to the stem loop structure of the histone mRNAs is required for this process. SLBP is also involved in regulation of histone mRNA nuclear export, degradation, and translation. Depletion of SLBP has been shown to induce polyadenylation of histone mRNAs and alteration of histone protein levels, which are considered to contribute to the observed aberrant cell cycle progress and genomic instability resulting from the loss of SLBP function. Recent studies have demonstrated that some heavy metal carcinogens, including arsenic and nickel, can induce the loss of SLBP and the gain of polyadenylation of canonical histone mRNAs. Polyadenylated canonical histone H3 can result in abnormal transcription, cell cycle arrest, genomic instability, and cell transformation, which links SLBP depletion and subsequent histone mRNA misprocessing to cancer. This review seeks to briefly summarize what is known about regulation of SLBP expression, consequences of SLBP depletion, its roles in cancer-related end points, with particular focus on metal-induced SLBP depletion and the potential of SLBP depletion as a new mechanism for metal-induced carcinogenesis.

Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with "Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline".

Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combating their harmful effects. Using the nematode Caenorhabditis elegans, a model with many genetic and physiological similarities to humans, researchers in the Colaiácovo laboratory have identified several molecular mechanisms by which the toxic agent bisphenol A (BPA) interferes with reproduction. Here, we address their recent discovery that a widely available compound, Coenzyme Q10 (CoQ10), can rescue BPA-induced damage. This work is significant in that it poses a low-cost method for improving reproductive success in humans. The goal of this primer is to assist educators and students with navigating the paper entitled "Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline." It is ideally suited for integration into an upper-level undergraduate course such as Genetics, Cell and Molecular Biology, Developmental Biology, or Toxicology. The primer provides background information on the history of BPA, the utility of the C. elegans germ line as a model for studying reproductive toxicity, and research methods including assessment of programmed cell death, fluorescent microscopy applications, and assays to quantify gene expression. Questions for deeper exploration in-class or online are provided.Related article in GENETICS: Hornos Carneiro MF, Shin N, Karthikraj R, Barbosa F Jr, Kannan K, Colaiácovo MP. Antioxidant CoQ10 restores fertility by rescuing bisphenol A-induced oxidative DNA damage in the Caenorhabditis elegans Germline. Genetics 214:381-395.

Neonicotinoid-containing insecticide disruption of growth, locomotion, and fertility in Caenorhabditis elegans.

Neonicotinoids, a class of insecticides structurally similar to nicotine that target biting and sucking insects, are the most widely used insecticides today, in part due to their supposed low toxicity in other organisms. However, a growing body of research has found that even low doses of neonicotinoids can induce unexpected negative effects on the physiology and survival of a wide range of non-target organisms. Importantly, no work has been done on the commercial formulations of pesticides that include imidacloprid as the active ingredient, but that also contain many other components. The present study examines the sublethal effects of "Tree and Shrub"™ ("T+S"), a commercial insecticide containing the neonicotinoid imidacloprid as its active ingredient, on Caenorhabditis elegans. We discovered that "T+S" significantly stunted the overall growth in wildtype nematodes, an effect that was exacerbated by concurrent exposure to heat stress. "T+S" also negatively impacted fecundity as measured by increased germline apoptosis, a decrease in egg-laying, and fewer viable offspring. Lastly, exposure to "T+S" resulted in degenerative changes in nicotinic cholinergic neurons in wildtype nematodes. As a whole, these findings demonstrate widespread toxic effects of neonicotinoids to critical functions in nematodes.