Bcl-rambo beta, a special splicing variant with an insertion of an Alu-like cassette, promotes etoposide- and Taxol-induced cell death

The exonization of an Alu-like element into a coding sequence is unique to primates and this phenomenon distinguishes our genome from other mammals. Here, we report the presence of a special splicing variant of a proapoptotic protein Bcl-rambo in human lymph node, designated as Bcl-rambo beta. This variant contains a 98 by Alu-like sequence which acts as an exon. There exists an in-frame stop codon within this inserted Alu-like cassette, resulting in generation of a premature protein of 104 amino acid residues. Unlike the Bcl-rambo, Bcl-rambo beta is lacking of the BH1, BH2 and BH3 motifs and becomes a BH4-only protein. Bcl-rambo beta is detected in several adult human tissues such as heart, lymph node and cervix but is absent in human brain tissue. In addition, Bcl-rambo beta is found not to be associated with mitochondria due to the absence of its C-terminal membrane anchor region. Nevertheless, this cytosol-localized protein is capable of promoting etoposide and Taxol-induced cell death. Although the exact function of the Alu sequence is not fully characterized, the Alu element within the Bcl-rambo beta appeared to contribute to the proapoptotic capability, since removing of the Alu sequence from Bcl-rambo beta abrogates its ability to induce cell death. Our data support the speculation that the Alu element insertion during the splicing process may play an important role in the generation of protein diversity in primate cells by a yet uncharacterized mechanism. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.