The fate of U1 snRNP during anti-Fas induced apoptosis: specific cleavage of the U1 snRNA molecule

During apoptosis, the U1-70K protein, a component of the spliceosomal U1 sn RNP complex, is specifically cleaved by the enzyme caspase-3, converting it into a C-terminally truncated 40-kDa fragment. In this study, we show that the 40-kDa U1-70K fragment is still associated with the complete U1 snRNP complex, and that no obvious modifications occur with the U1 snRNP associat ed proteins U1A, U1C and Sm-B/B'. Furthermore, it is described for the firs t time that the U1 snRNA molecule, which is the backbone of the U1 snRNP co mplex, is modified during apoptosis by the specific removal of the first 5- 6 nucleotides including the 2,2,7-trimethylguanosine (TMG) cap. The observa tions that U1 snRNA cleavage is very specific (no such modifications were d etected for the other U snRNAs tested) and that U1 snRNA cleavage is marked ly inhibited in the presence of caspase inhibitors, indicate that an apopto tically activated ribonuclease is responsible for the specific modification of U1 snRNA during apoptosis.