Functional non-coding ncRNA in immunity and tolerance: what can be learned from structures and functions of transfer factors of delayed-type[-IV] hypersensititvity on genetics, epigenetics and recognition repertoires (62.12)

Abstract

Abstract AIM: Immunity and [self-]tolerance are usually considered orchestrated by protein repertoires upon genetic [Mendelian] and epigenetic [non-Mendelian] variation mechanisms. All is still not fully understood, as evident from transfer factor and LeDouarin phenomena, environmental influences, peptidome complexity and diversity [Adv.Immunol.11,195-266,1969; Int.J.Dev.Biol.49,131-136,2005]. Endogenous ncRNA incl. microRNA mostly escaped consideration. METHODS: Ann.N.Y.Acad.Sci.1137,316-342,2008. RESULTS: Landsteiner-Chase-Lawrence transfer factors showed up as paradigmatic guides in some terra incognita of adaptive immune memory. Original crude preparations were found as paucidisperse solute systems of numerous functional small ncRNA [<200n] in interaction with proteins. Some environment-modified redox- and metalloregulated small hairpin shRNA [<200 bases] were sequenced. By 5'-CUG-3’-hairpin loops, they may address conserved homologous helix-nucleating domains shared in self and foreign proteofactors of tolerated growth, metabolism, vascularization, cancer and epigenome indexing. CONCLUSIONS: Immune cells are not restricted to known protein recognition systems. They have further repertoires of environment-adapted ncRNA as earliest outputs in transcription and translation. These are superior in diversity/specificity [≥10E17] to immune proteins repertoires [~10E13]. All attributes make them competent to integrate information flow on possible molecular shapes into genomic mechanisms.