INHIBITION BY SR PROTEINS OF SPLICING OF A REGULATED ADENOVIRUS PRE-MESSENGER-RNA

THE adenovirus L1 unit(1) represents an example of an alternatively sp liced precursor messenger (pre-mRNA) where one 5' splice can be joined to one of two alternative 3' splice sites, producing the 52,55K or th e IIIa mRNAs (Fig, 1a). Efficient usage of the distal IIIa 3' splice s ite requires late viral protein synthesis and is therefore confined to the late phase of virus infection(2-4). Here we show that, in extract s from uninfected cells, the classical SR proteins(5), which are essen tial splicing factors(5-7), inhibit IIIa pre-mRNA splicing by binding to an intronic repressor element and preventing recruitment of the U2 small nuclear ribonucleoprotein particle to the spliceosome. We furthe r show that the viral repressor element has splicing-enhancer activity when appropriately placed in the pre-mRNA. Together, our results demo nstrate that SR proteins function as activators or repressors of splic ing depending on where on the pre-mRNA they bind.