Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes

The 26S proteasome is a multisubunit protein-destroying machinery that degr ades ubiquitin-tagged proteins. To date only a single species of Rpn10, whi ch possibly functions as a multiubiquitin chain-binding subunit, has been i dentified in various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single gene by developmentally regulated, alternative spl icing. Rpn10a is ubiquitously expressed, whereas Rpn10e is expressed only i n embryos, with the highest levels of expression in the brain. Both forms o f Rpn10 are components of the 26S proteasome, with an apparently similar af finity for multiubiquitylated [I-125]lysozyme in vitro. However, they exert markedly divergent effects on the destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome occurs in at least two functionally distinct forms: one containing a ubiquitously expressed Rpn10a and the othe r a newly identified, embryo-specific Rpn10e. While the former is thought t o perform proteolysis constitutively in a,vide variety of cells, the latter may play a specialized role in early embryonic development.