Transcription termination and 3 end formation are essential processes necessary for gene expression. However, the specific mechanisms responsible for these events remain elusive. A screen designed to identify trans-acting factors involved in these mechanisms in Saccharomyces cerevisiae identified a temperature-sensitive mutant that displayed phenotypes consistent with a role in transcription termination. The complementing gene was identified as GRS1, which encodes the S. cerevisiae glycyl-tRNA synthetase. This result, although unusual, is not unprecedented given that the involvement of tRNA synthetases in a variety of cellular processes other than translation has been well established. A direct role for the synthetase in transcription termination was determined through several in vitro assays using purified wild type and mutant enzyme. First, binding to two well characterized yeast mRNA 3 ends was demonstrated by cross-linking studies. In addition, it was found that all three substrates compete with each other for binding to GlyRS enzyme. Next, the affinity of the synthetase for the two mRNA 3 ends was found to be similar to that of its "natural" substrate, glycine tRNA in a nitrocellulose filter binding assay. The effect of the grs1-1 mutation was also examined and found to significantly reduce the affinity of the enzyme for the three RNA substrates. Taken together, these data indicate that not only does this synthetase interact with several different RNA substrates, but also that these substrates bind to the same site. These results establish a direct role for GRS1 in mRNA 3 end formation.The formation of a eukaryotic mRNA 3Ј end is a complex process involving factors that recognize, cleave, and process the pre-mRNA as well as those that facilitate the dissociation of RNA polymerase II from the DNA template. Although many of these factors have been identified, a comprehensive model of how the termination event interfaces with the processing activities remains elusive. The favored model suggests that termination is dependent on the recognition of a polyadenylation signal that then triggers a change in the polymerase, resulting in dissociation of the enzyme, followed by the termination event(s) (1). The most likely alteration in the actively transcribing enzyme would be a result of the "offloading" of 3Ј end processing factors that associate with the carboxyl-terminal domain of the largest subunit of RNAP II.

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Background: One of the greatest challenges in healthcare today is dealing with a growing burden of multimorbid chronic diseases in an aging population. Awareness is growing that a healthy start in life plays a critical role in reversing this trend, especially for young women, pregnant mothers, and children in their first 2 years of life. Methods: We reviewed the international literature on early childhood nutrition and development, based on the landmark Lancet series on maternal and child nutrition and child development, and World Health Organization reports. Results: Contemporary literature points to the importance of strategies that focus on early childhood for enhancing both health and socioeconomic outcomes. We discuss programs and initiatives that aim to improve the health of mothers and children at a global level, with a focus on high-income countries such as Australia and the United States. Conclusion: Tackling the epidemic of chronic diseases requires a comprehensive life course approach that must include pregnant women and their young children. Healthcare systems and professionals play an important role. The health and well-being of the next generation must be everyone's business.