Rapid nucleolytic degradation of the small cytoplasmic Y RNAs during apoptosis.
We have investigated the fate of the RNA components of small ribonucleoprotein particles in apoptotic cells. We show that the cytoplasmic Ro ribonucleoprotein-associated Y RNAs are specifically and rapidly degraded during apoptosis via a caspase-dependent mechanism. This is the first study describing the selective degradation of a specific class of small structural RNA molecules in apoptotic cells. Cleavage and subsequent truncation of Y RNAs was observed upon exposure of cells to a variety of apoptotic stimuli and were found to be inhibited by Bcl-2, zinc, and several caspase inhibitors. These results indicate that apoptotic degradation of Y RNAs is dependent on caspase activation, which suggests that the nucleolytic activity responsible for hY RNA degradation is activated downstream of the caspase cascade. The Y RNA degradation products remain bound by the Ro60 protein and in part also by the La protein, the only two proteins known to be stably associated with intact Ro ribonucleoprotein particles. The size of the Y RNA degradation products is consistent with the protection from degradation of the most highly conserved region of the Y RNAs by the bound Ro60 and La proteins. Our results indicate that the rapid abrogation of the yet unknown function of Y RNAs might be an early step in the systemic deactivation of the dying cell.
Rutjes
S A
SA
Department of Biochemistry, University of Nijmegen, P. O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
van der Heijden
A
A
Utz
P J
PJ
van Venrooij
W J
WJ
Pruijn
G J
GJ
D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis; D001324:Autoantigens / Q000378:metabolism; D001483:Base Sequence; D061945:Caspase Inhibitors; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D000841:Anisomycin; D001324:Autoantigens; D061945:Caspase Inhibitors; D003609:Dactinomycin; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012313:RNA; D016372:RNA, Antisense; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D015032:Zinc; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human