ASSOCIATION OF PHOSPHORYLATED SERINE ARGININE (SR) SPLICING FACTORS WITH THE U1-SMALL RIBONUCLEOPROTEIN (SNRNP) AUTOANTIGEN COMPLEX ACCOMPANIES APOPTOTIC CELL-DEATH/

Proteins subject to proteolysis or phosphorylation during apoptosis ar e commonly precipitated by autoantibodies found in the serum of patien ts with systemic lupus erythematosus (SLE). We screened a panel of mur ine monoclonal and human monospecific sera reactive with known autoant igens for their ability to selectively precipitate phosphoproteins fro m apoptotic Jurkat T cell lysates. Sera known to recognize the U1-smal l nuclear ribonucleoprotein (snRNP) complex (confirmed by their abilit y to precipitate U1-snRNA) selectively precipitated a phosphoprotein c omplex (pp54, pp42, py34, and pp23) from apoptotic lysates. Monoclonal antibodies reactive with U1-snRNP proteins precipitated the same phos phoprotein complex from apoptotic lysates. The phosphorylation and/or recruitment of these proteins to the U1-snRNP complex is induced by mu ltiple apoptotic stimuli (e.g., Fas ligation, gamma irradiation or UV irradiation), and is blocked by overexpression of bcl-2. The U1-snRNP- associated phosphoprotein complex is immunoprecipitated by monoclonal antibodies reactive with serine/arginine (SR) proteins that comprise a structurally related family of splicing factors. The association of p hosphorylated SR proteins with the U1-snRNP complex in cells undergoin g apoptosis suggests a mechanism for regulation of alternative splicin g of apoptotic effector molecules.