THE HUMAN U1A SNRNP PROTEIN REGULATES POLYADENYLATION VIA A DIRECT INTERACTION WITH POLY(A) POLYMERASE

The human U1 snRNP-specific U1A protein autoregulates its production b y binding its own pre-mRNA and inhibiting polyadenylation. The mechani sm of this regulation has been elucidated by in vitro studies. U1A pro tein is shown not to prevent either binding of cleavage and polyadenyl ation specificity factor (CPSF) to its recognition sequence (AUUAAA) o r to prevent cleavage of U1A pre-mRNA. Instead, U1A protein bound to U 1A pre-mRNA inhibits both specific and nonspecific polyadenylation by mammalian, but not by yeast, poly(A) polymerase (PAP). Domains are ide ntified in both proteins whose removal uncouples the polyadenylation a ctivity of mammalian PAP from its inhibition via RNA-bound U1A protein . Finally, U1A protein is shown to specifically interact with mammalia n PAP in vitro. The possibility that this interaction may reflect a br oader role of the U1A protein in polyadenylation is discussed.