DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0063
Abstracts
45
This anti-U 1 RNA patient serum also contains antibodies that react with the
U1 snRNP-associated A protein. The A protein may bind to U1 RNA at the same
or a similar site as does the U 1 RNA-specific antibody. If this is true, the A prote-
in and the U1 RNA-specific antibody should overlap and compete with one
another for binding to the RNA. To examine this question, we have shown that
the A protein will bind to U1 RNA in the absence of any other protein. We report
the binding of the 32 kD A protein to stem-loop II of U 1 RNA (nucleotides
49-85) as determined by Northwestern blotting assays and soluble protein in
vitro binding assays (Lutz-Freyermuth and Keene, Mol. Cell Biol., in press).
This binding site of the A protein on U 1 RNA is found in a region with similarity
to U 2 RNA. The region of similarity in U 2 RNA exists in a region that has been
proposed to interact with a U2-associated protein, B" (Mattaj and De Rober-
TIS, 1985, Cell 40:111-118). Proteins A and B" are very similar at the amino
acid level (Sillekens et al., 1987, EMBO J. 12:3841-3848), and each contains
two repeats of a proposed RNA recognition motif (RRM) that are likely to be in-
volved in RNA binding. These findings suggest that structural similarities shared
by U1 and U 2 snRNPs may be involved in RNA-protein interactions within the
spliceosome. Thus, we have shown that the A protein and the anti-U 1 RNA an-
tibody share overlapping binding sites on U1 RNA. These findings may have im-
portant implications for anti-idiotypic models of autoimmunity.
Anti-Ribosomal P Protein Antigens and Antibodies
J. Magsaam1, H. Weissbach2, N. Brot2, and K. B. Elkon’
'The Hospital for Special Surgery, Cornell Medical Center 535 East 70th Street,
New York, NY 10021, USA
2Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110, USA
Approximately 12% of patients with SLE have anti-P and the presence of this
antibody is relatively specific for the disease. A similar percentage (10%) of
MRL/lpr mice, but not BXSB or NZB/W mice, also have anti-P antibodies. In
humans with SLE, the presence of anti-P is strongly associated with a clinical
subset of neuropsychiatric lupus.
The fine specificity of anti-P antibodies has been mapped by partial pro-
teolysis, synthetic peptides and deletion mutants of a cDNA encoding the P2 pro-
tein. The results of these studies indicate that (i) there are linear and conforma-
tional epitope(s), (ii) there is a single linear epitope located within the C-terminal
45
This anti-U 1 RNA patient serum also contains antibodies that react with the
U1 snRNP-associated A protein. The A protein may bind to U1 RNA at the same
or a similar site as does the U 1 RNA-specific antibody. If this is true, the A prote-
in and the U1 RNA-specific antibody should overlap and compete with one
another for binding to the RNA. To examine this question, we have shown that
the A protein will bind to U1 RNA in the absence of any other protein. We report
the binding of the 32 kD A protein to stem-loop II of U 1 RNA (nucleotides
49-85) as determined by Northwestern blotting assays and soluble protein in
vitro binding assays (Lutz-Freyermuth and Keene, Mol. Cell Biol., in press).
This binding site of the A protein on U 1 RNA is found in a region with similarity
to U 2 RNA. The region of similarity in U 2 RNA exists in a region that has been
proposed to interact with a U2-associated protein, B" (Mattaj and De Rober-
TIS, 1985, Cell 40:111-118). Proteins A and B" are very similar at the amino
acid level (Sillekens et al., 1987, EMBO J. 12:3841-3848), and each contains
two repeats of a proposed RNA recognition motif (RRM) that are likely to be in-
volved in RNA binding. These findings suggest that structural similarities shared
by U1 and U 2 snRNPs may be involved in RNA-protein interactions within the
spliceosome. Thus, we have shown that the A protein and the anti-U 1 RNA an-
tibody share overlapping binding sites on U1 RNA. These findings may have im-
portant implications for anti-idiotypic models of autoimmunity.
Anti-Ribosomal P Protein Antigens and Antibodies
J. Magsaam1, H. Weissbach2, N. Brot2, and K. B. Elkon’
'The Hospital for Special Surgery, Cornell Medical Center 535 East 70th Street,
New York, NY 10021, USA
2Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110, USA
Approximately 12% of patients with SLE have anti-P and the presence of this
antibody is relatively specific for the disease. A similar percentage (10%) of
MRL/lpr mice, but not BXSB or NZB/W mice, also have anti-P antibodies. In
humans with SLE, the presence of anti-P is strongly associated with a clinical
subset of neuropsychiatric lupus.
The fine specificity of anti-P antibodies has been mapped by partial pro-
teolysis, synthetic peptides and deletion mutants of a cDNA encoding the P2 pro-
tein. The results of these studies indicate that (i) there are linear and conforma-
tional epitope(s), (ii) there is a single linear epitope located within the C-terminal