Functional Somatic Noncoding ncRNA of Extracelular Vesicles [EV] for Vascular Epigenetics: A Genomic Crossword Puzzle in Adaptation of Cells under Stress
Authors: Wissler Josef H. 
Published: June 2021

OBJECTIVEFormation, remodeling and adaptation of different blood and lymphatic vessel phenotypes result from vasculo‐, angio‐, arterio‐ and lymph‐angiogenesis by complex interplay of various cells and factors [proteins, RNA, metal ions, metabolites, hormones, environment, stress]. Beyond genetics, by vascular epigenetics, diversity, complexity and tolerance of vascular phenotypes are vice versa requisites for function and survival of networked cells with interfaces upon intrinsic and extrinsic [environmental] needs and changes. It may be manifested beneficial or maladaptive entangled with, e.g. development, healing, implants, cardiovascular, immune or cancer‐angiogenesis‐tolerance reactions. This investigation aimed at whether formation and structure of some angio‐morphogen RNA sequences are from inherited germline [Mendelian] origin or somatic non‐Mendelian derivatives. The latter are functional RNA which retranslation do not anymore fit to inherited genes.METHODSFor search, angiotropin‐related RNA [ARNA] and MIR126 genes of microRNA‐126 [miR‐126] structures were used.RESULTSmiR‐126 are small Mendelian split products of MIR126 genes. Angiotropin is one of several exosomal RNP angiomorphogens from stressed mononuclear cells [shear, exercise stress, hypoxia, etc.]. It was sequenced after isolation from EV fluids where it is active in vitro and in tissue. By metal ions [Cu, Ca, Na, K], a Mendelian‐coded angiotropin‐related protein [S100‐A12] folds to a stable complex with somatic non‐Mendelian functional 5′end‐phosphorylated, edited, modified, redox‐ and metallo‐regulated non‐coding ARNA [75n] with 5′CUG3′‐hairpin loop. Its modified bases isoG/adenosine‐N1‐oxide are from Fenton‐type redox‐OH*/NO*‐radical RNA modification of adenosine in mesomeric/tautomeric complex with copper ions. It is shown that ARNA are formed by stressed mononuclear cells by rearrangement, recombination, mutation, editing, modification, redox‐ and metalloregulation of inherited MIR‐126 gene and its complementary derivative chain segments.CONCLUSIONSThe results suggest novel targets for vascular therapy. Some aspects of non‐Mendelian functional ncRNA resemble the process of somatic generation of immune diversity, as shown by Tonegawa. In this special case, all is achieved on the DNA and mRNA level, namely for coding new [immune] proteins by somatic cells under antigen attack stress. Here, a general principle is disclosed operated by somatic cells under stress on all nucleic acid, protein and carbohydrate levels to manage any diversity and complexity problems with their limited set of the inherited DNA in response to environmental chance reactions. New non‐Mendelian functional somatic noncoding RNA sequences for vascular epigenetics result from a genomic crossword puzzle by combined mechanisms of rearrangement, recombination, mutation, editing, modification, redox‐ and metalloregulation of inherited ncRNA of genes and their complementary derivative chain segments, i.e. by shuffling together segments of gene ncRNA and reuse of its non‐coding complementary sequence for tissue survival and adaptation to extraordinary environmental stress situations.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.