SPECIFIC CLEAVAGE OF THE 70-KDA PROTEIN-COMPONENT OF THE U1 SMALL NUCLEAR RIBONUCLEOPROTEIN IS A CHARACTERISTIC BIOCHEMICAL FEATURE OF APOPTOTIC CELL-DEATH

The U1 small nuclear ribonucleoprotein particle is essential for splic ing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kD a protein (U1-70kDa). We report here that U1-70kDa is specifically cle aved in apoptotic cells, resulting in the generation of a 40-kDa fragm ent. The kinetics of this cleavage coincided with the appearance of ce lls with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells th at had become detached from the substratum. Although the inhibitor cha racteristics of the activity cleaving U1-70kDa suggest that interleuki n 1 beta-converting enzyme (ICE) might be responsible, the specific IC E inhibitor N-(N-acetyl-tyrosinylvalinyl-alaninyl)- 3-amino-4-oxobutan oic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cle aved by purified ICE in vitro. Further study of this novel cleavage an d the enzyme responsible will yield information about proteolytic even ts that might be central in the mechanism and control of apoptosis.