{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T19:24:03Z","timestamp":1700076243271},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":590,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Bioassays for cellular differentiation and tissue morphogenesis were used to design methods for isolation of bioactive redox\u2010 and metalloregulated nucleic acids and copper ion complexes with proteins from extracellular, circulating, wound, and supernatant fluids of cultured cells. In extracellular biospheres, diversities of nucleic acids were found to be secreted by cells upon activation. They may reflect nucleic acid biolibraries with molecular imprints of cellular history. After removal of protein components, eRNA prototypes exuded by activated cells were sequenced. They are small, endogenous, highly modified and edited, redox\u2010 and metalloregulated 5\u2032\u2010end phosphorylated extracellular eRNA (\u223c2\u2013200 bases) with cellular, enzymic, and bioaptamer functions. Fenton\u2010type OH* radical redox reactions may form modified nucleotides in RNA as wobbles eRNA per se, or as copper ion\u2010complex with protein (e.g., S100A12\u2010EF\u2010hand protein, angiotropin\u2010related protein, calgranulin\u2010C, hippocampal neurite differentiation factor) are shown to be bioactive <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> as cytokines (ribokines) and as nonmitogenic angiomorphogens for endothelial cell differentiation in the formation of organoid supracellular capillary structures. As bioaptamers, copper ion\u2010structured eRNA imparts novel biofunctions to proteins that they do not have on their own. The origin of extracellular RNA and intermediate precursors (up to 500 bases) was traced to intracellular parent nucleic acids. Intermediate precursors with and without partial homology were found. This suggests that bioaptamers are not directly retranslatable gene products. Metalloregulated eRNA bioaptamer function was investigated by domains (e.g. <jats:sup>5\u2032<\/jats:sup>\u2026CUG\u2026<jats:sup>3\u2032<\/jats:sup> hairpin loop) for folding, bioactivity, and binding of protein with copper, calcium, and alkali metal ion affinity. Vice versa, metalloregulated nucleic acid\u2010binding domains (K3H, R3H) in proteins were identified. Interaction of protein and eRNA docking potentials were visualized by 3D\u2010rapid prototyping of accurate molecular image models based on crystallographic or NMR data. For S100A12\u2010homologous proteins, receptor\u2010 and metalloregulated RNA chaperone\u2010shaped protein assemblies were investigated. They suggest insight into signaling cascades as to how eRNA transmits its cytokine (ribokine) bioinformation from the extracellular RNA biosphere into cells. Proteomics of the extracellular RNA biosphere demonstrate the presence of nucleic acid\u2010binding domain homologies in defense\u2010, aging\u2010, and disease\u2010associated neuronal and other proteins as targets for RNA orphans. By structural relationships found to transmissible processes, proteinaceous transfer (\u201cinfectivity\u201d) and feedback of bioinformation beyond the central dogma of molecular biology are considered in terms of metalloregulated RNA bioaptamer function, nucleic acid\u2010binding domains, and protein conformation.<\/jats:p>","DOI":"10.1196\/annals.1318.027","type":"journal-article","created":{"date-parts":[[2004,7,13]],"date-time":"2004-07-13T23:44:51Z","timestamp":1089762291000},"page":"163-184","source":"Crossref","is-referenced-by-count":6,"title":["Extracellular and Circulating Redox\u2010 and Metalloregulated eRNA and eRNP: Copper Ion\u2010Structured RNA Cytokines (Angiotropin Ribokines) and Bioaptamer Targets Imparting RNA Chaperone and Novel Biofunctions to S100\u2010EF\u2010Hand and Disease\u2010Associated Proteins"],"prefix":"10.1111","volume":"1022","author":[{"given":"JOSEF H.","family":"WISSLER","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,7,8]]},"reference":[{"key":"e_1_2_5_2_2","unstructured":"Gesteland R.F. 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Inflammatory mediators and wound hormones: Chemical signals for differentiation and morphogenesis in tissue regeneration and healing.InProceedings of the 33th Mosbach Colloquium 1982: Biochemistry of Differentiation and Morphogenesis. L. Jaenicke Ed.: 257\u2013274. Springer Verlag. Heidelberg Germany.","DOI":"10.1007\/978-3-642-68833-1_24"},{"key":"e_1_2_5_13_2","unstructured":"Wissler J.H. 1984. Large scale and biotechniques for the production and isolation of leucocytic effector substances of regenerative tissue morphogenesis by culturing cells in serum\u2010free synthetic fluids: Design preparation and use of a novel medium.InDevelopments in Nuclear Medicine Vol. 7: Blood Cells in Nuclear Medicine Part 2: Migratory Blood Cells. G.F. Fueger Ed.:41\u2013102 & 393\u2013471. Martinus Nijhoff Publishers. Boston."},{"key":"e_1_2_5_14_2","unstructured":"Wissler J.H. E. Logemann H.E. Meyer et al.1986. Structure and function of a monocytic blood vessel morphogen (angiotropin) for angiogenesis in vivo and in vitro: a copper\u2010containing metallo\u2010polyribonucleo\u2010polypeptide as a novel and unique type of monokine.InProtides of the Biological Fluids. H. Peeters Ed. 34: 517\u2013536. Pergamon Press. Oxford."},{"key":"e_1_2_5_15_2","unstructured":"Wissler J.H. H. Renner & E. Logemann. 1989. Mechanisms in neovascularization of avascular ocular tissue by a monocytic angio\u2010morphogen.InModern Trends in Immunology and Immunopathology of the Eye. A.G. Secchi & I.A. Fregona Eds.:174\u2013188. Masson. 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