THE HUMAN U1 SNRNP-SPECIFIC U1A PROTEIN INHIBITS POLYADENYLATION OF ITS OWN PREMESSENGER RNA

Human, mouse, and Xenopus mRNAs encoding the U1 snRNP-specific U1A protein contain a conserved 47 nt region in their 3' untranslated regions (UTRs). In vitro studies show that human U1A protein binds to two sites within the conserved region that resemble, in part, the previously characterized U1A-binding site on U1 snRNA. Overexpression of human U1A protein in mouse cells results in down-regulation of endogenous mouse U1A mRNA accumulation. In vitro and in vivo experiments demonstrate that excess U1A protein specifically inhibits polyadenylation of pre-mRNAs that contain the conserved 3' UTR from human U1A mRNA. Thus, U1A protein regulates the production of its own mRNA via a mechanism that involves pre-mRNA binding and inhibition of polyadenylation.