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MicroRNA as bioaptamers in RNP cytokines [ribokines] and codes for epigenetic phenotype alterations and self‐tolerance: Sequence‐defined endogenous redox‐ and metalloregulated, edited and modified “non‐coding” small hairpin RNA
Author(s) -
Wissler Josef H.,
Wissler Joerg E.,
Logemann Enno
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a930-d
Subject(s) - epigenetics , rna , gene , chemistry , microrna , microbiology and biotechnology , phenotype , biology , genetics
Mammalian miRNA roles were investigated in epigenetic [non‐Mendelian] phenotype alterations [EPA] in cells and protein conformations in self‐tolerance and discrimination of damaged self‐ and intruded foreign matter by sustaining and obliterating abnormal hypervascular patterns [Wissler et al., Protides Biol. Fluids 34 : 517‐536, 1986; Materialwiss. Werkstofftech. 32 : 984‐1008, 2001; Arch. Surg. 124 : 693‐698, 1989; Ann. N.Y. Acad. Sci. 961 : 292‐297, 2002; 991 : 333‐338, 2003; 1022 : 163‐184, 2004; FASEB J. 19 : A621, 2005; FEBS J. 272‐s1 : N1‐06‐4P, 2005; Mol. Biol. Cell Suppl. 12 : 149a‐150a, 2001; 16: # 1459 & 2848, 2005]. Bioactive metalloregulated complexes of entitled RNA bioaptamers [<200 bases] and protein conformers were isolated from cells, supernatants and wound fluids. By Cu ion‐structured 5′ ‐CUG‐ 3′ hairpin loops, such RNA fit to binding domains in epigenetic regulator proteins [e.g. angiotropin angio‐morphogens], termed K/R3H [K/RxxxH], i.e. ‐t/s/xK/R/q/nxxxH/y/n/q/e/dx 7‐9 h/xx 7‐9 h/xx 5‐20 K/R/q/n/e/h‐ with accessory basic [R/K] n , R/K‐zipper, SR/K/RS and / or HxxxH/y/n/q segments. By sequence edition, base modification [e.g. to isoguanine], redox‐ and metalloregulation, i.e. code extensions / alterations, some RNA are not directly retranslatable to heritable genome codes but feedback protein folding to translation and transcription. The results suggest such RNA part of specific clonal recognition in novel EPA, inheritance and cancer escape mechanisms in RNA‐operated conformation phase pathway‐locked loops. They are comparably effective as antibody [~10 8 ], T‐cell receptor [~10 10 ] and MHC systems [~10 13 ] but superior in diversity / specificity [estimated repertoire ~10 17 ].