The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as the "fifth" ribonucleotide in 1951. Since then, the ever-increasing number and complexity of modified ribonucleosides have been found in viruses and throughout all three domains of life. Such modifications can be as simple as methylations, hydroxylations, or thiolations, complex as ring closures, glycosylations, acylations, or aminoacylations, or unusual as the incorporation of selenium. While initially found in transfer and ribosomal RNAs, modifications also exist in messenger RNAs and noncoding RNAs. Modifications have profound cellular outcomes at various levels, such as altering RNA structure or being essential for cell survival or organism viability. The aberrant presence or absence of RNA modifications can lead to human disease, ranging from cancer to various metabolic and developmental illnesses such as Hoyeraal-Hreidarsson syndrome, Bowen-Conradi syndrome, or Williams-Beuren syndrome. In this review article, we summarize the characterization of all 143 currently known modified ribonucleosides by describing their taxonomic distributions, the enzymes that generate the modifications, and any implications in cellular processes, RNA structure, and disease. We also highlight areas of active research, such as specific RNAs that contain a particular type of modification as well as methodologies used to identify novel RNA modifications.

Background and Hypothesis:  Lead (Pb) was phased out of paint and gasoline over 40 years ago due to neurotoxicity in humans, but has persisted in soils and poses a legacy threat to many.  The Indianapolis 46218 zip code has had >10% children exhibiting Pb poisoning. This zip code has had historically high soil Pb levels, and is undergoing redevelopment. We hypothesize that redevelopment will act to re-expose new populations of people to the legacy Pb present in the area.    Experimental Design or Project Methods:  We sampled 5 parks and 7 playgrounds.  Stratified random sampling based on permit type was used to select properties from 25 issued and 25 closed permits from 527 identified demolition permits.  Nearby residential properties were selected, with permission of residents. Samples were taken near the dripline of the house, front yard, and street, or from each quadrant at sites without houses. Samples were dried, crushed, sieved to 150 microns, and assessed using X-Ray Fluorescence.    Results:  Mean Pb levels from driplines (1026 ppm) were significantly higher than streets (p=0.001), parks (p=0.002), yards (p=0.001), and demolition sites (p=0.000).  Pb concentrations for playgrounds had the lowest median lead levels (42 ppm), while dripline samples had the highest (289 ppm).  The EPA standard for children’s play areas is 400 ppm.  Conclusion and Potential Impact:  While all samples from playgrounds were below 400 ppm, children are also likely playing at their homes, where no legislation effectively protects them from potential Pb poisoning and values were found above 400 ppm.  An immediate outcome from this project is the education.  Residents who agreed to testing (n=42) received results of the test and guidelines to prevent Pb poisoning.  More work remains to ensure preventive rather than reactive strategies are employed to protect children’s health.

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