Abstract

Keywords

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

WGJ Degen¹, Y van Aarssen¹, GJM Pruijn¹, PJ Utz² & WJ van Venrooij¹

Correspondence to: WGJ Degen, Department of Biochemistry, University of Nijmegen, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands. Tel: (+31) 24 361 4253; Fax: (+31) 24 354 0525; E-mail: w.degen@bioch.kun.nl

Edited by A Strasser

During apoptosis, the U1-70K protein, a component of the spliceosomal U1 snRNP 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 associated proteins U1A, U1C and Sm-B/B’. Furthermore, it is described for the first time that the U1 snRNA molecule, which is the backbone of the U1 snRNP complex, is modified during apoptosis by the specific removal of the first 5 – 6 nucleotides including the 2,2,7-trimethylguanosine (TMG) cap. The observations that U1 snRNA cleavage is very specific (no such modifications were detected for the other U snRNAs tested) and that U1 snRNA cleavage is markedly inhibited in the presence of caspase inhibitors, indicate that an apoptotically activated ribonuclease is responsible for the specific modification of U1 snRNA during apoptosis. Cell Death and Differentiation (2000) 7, 70 – 79.

^© Macmillan Publishers Ltd 2000