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001-es BibID:BIBFORM053872
Első szerző:Bachmann, Michael
Cím:Autoimmunity as a result of escape from RNA surveillance / Michael P. Bachmann, Holger Bartsch, Joanne K. Gross, Shannon M. Maier, Timothy F. Gross, Jennifer L. Workman, Judith A. James, A. Darise Farris, Bettina Jung, Claudia Franke, Karsten Conrad, Marc Schmitz, Cordula Büttner, Jill P. Buyon, Imre Semsei, John B. Harley, E. Peter Rieber
Dátum:2006
ISSN:0022-1767 1550-6606
Megjegyzések:In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in approximately 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Immunology. - 177 : 3 (2006), p. 1698-1707. -
További szerzők:Bartsch, Holger Gross, Joanne K. Maier, Shannon Gross, Timothy F. Workman, Jennifer L. James, Judith A. Farris, Darise Jung, Bettina Franke, Claudia Conrad, Karsten Schmitz, Marc Buttner, Cordula Buyon, Jill P. Semsei Imre (1954-) (vegyész, gerontológus) Harley, John B. Rieber, E. Peter
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