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Prokaryotic SPHINX 1.8 REP protein is tissue‐specific and expressed in human germline cells
Author(s) -
Manuelidis Laura
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27907
Subject(s) - biology , scrapie , open reading frame , somatic cell , germline , sphinx , neurodegeneration , microbiology and biotechnology , virology , cytoplasm , genetics , gene , peptide sequence , disease , prion protein , medicine , art , pathology , visual arts
Small circular DNAs of 1.8 and 2.4 kb were initially discovered in highly infectious Creutzfeldt‐Jakob Disease (CJD) and scrapie particles from mammalian brain and cultured cells. Surprisingly, these protected cytoplasmic "SPHINX" DNAs contained replication (REP) initiation sequences resembling those of Acinetobacter phage viruses. An antibody was generated against a REP peptide encoded by the SPHINX 1.8 open reading frame (ORF) that was not present in mammals. It bound to a 41kd “spx1” protein on Western blots. Cytologically, spx1 concentrated in spinal cord synapses and pancreatic islet, but not exocrine cells. We hypothesized that circular SPHINX DNAs are ancient symbiotic elements that can participate in functional differentiation and neurodegeneration. Cell and tissue‐specific patterns of spx1 expression shown below implicate somatic cell‐to‐cell communication and differentiation functions that would favor conservation of SPHINX 1.8 in evolution. Remarkably, primary human oocytes and spermatogonia, but not mature sperm, displayed intense cytoplasmic spx1 signals that underscore the maternal inheritance of SPHINX 1.8. These findings should encourage investigations of unexplored networks of incorporated environmental infectious agents that can be key actors in progressive neurodegeneration, immunity, and cancer.