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Caspase-dependent cleavage of nucleic acids
W G Degen1, G J Pruijn, J M Raats
1Department of Biochemistry, University of Nijmegen, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Abstract:
Autoimmune diseases are frequently characterized by the presence of autoantibodies directed against nucleic acid-protein complexes present in the nucleus of the cell. The mechanisms by which these autoantigenic molecules escape immunological tolerance are largely unknown, although a number of recent observations suggest that modified self-proteins generated during apoptosis may play an important role in the development of autoimmunity. It has been hypothesized that the recognition of these modified self-proteins by the immune system may promote autoantibody production. While apoptosis is specifically characterized by posttranslational modification of proteins, recent findings also show that nucleic acids are modified. This review summarizes the specific cleavages of some of these key nucleic acids, i.e. chromosomal DNA, ribosomal RNA and small structural RNAs (U1 snRNA, Y RNA), in apoptotic cells.
Insights
Modified nucleic acids in apoptotic cells may trigger autoimmune diseases by escaping immune tolerance. This review details specific nucleic acid cleavages during apoptosis, potentially driving autoantibody production.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Autoimmune diseases often involve autoantibodies targeting nuclear nucleic acid-protein complexes.
- Mechanisms of immune tolerance escape in autoimmunity are poorly understood.
- Modified self-proteins during apoptosis are implicated in autoimmunity development.
Purpose of the Study:
- To review the specific cleavages of key nucleic acids during apoptosis.
- To explore the role of modified nucleic acids in the development of autoimmunity.
Main Methods:
- Literature review of studies on apoptosis and nucleic acid modifications.
- Analysis of specific nucleic acid cleavages: chromosomal DNA, ribosomal RNA, U1 snRNA, and Y RNA.
Main Results:
- Apoptosis involves posttranslational modification of proteins and modification of nucleic acids.
- Specific cleavages of chromosomal DNA, ribosomal RNA, U1 snRNA, and Y RNA occur in apoptotic cells.
Conclusions:
- Modified nucleic acids generated during apoptosis may contribute to the breakdown of immunological tolerance.
- Recognition of these modified nucleic acids could promote autoantibody production in autoimmune diseases.