U1 SNRNP INHIBITS PRE-MESSENGER-RNA POLYADENYLATION THROUGH A DIRECT INTERACTION BETWEEN U1 70K AND POLY(A) POLYMERASE

It has previously been shown in vivo that bovine papillomavirus repres ses its late gene expression via a 5' splice site sequence located ups tream of the late polyadenylation signal. Here, the mechanism of repre ssion is determined by in vitro analysis. U1 snRNP binding to the 5' s plice site results in inhibition of polyadenylation via a direct inter action with poly(A) polymerase (PAP). Although the inhibitory mechanis m is similar to that used in U1A autoregulation, U1A within the U1 snR NP does not contribute to PAP inhibition. Instead the U1 70K protein, when bound to U1 snRNA, both interacts with and inhibits PAP. Conserva tion of the U1 70K inhibitory domains suggests that polyadenylation re gulation via PAP inhibition may be more widespread than previously tho ught.