The poly(A)-limiting element is a conserved cis-acting sequence that regulates poly(A) tail length on nuclear pre-mRNAs

Most vertebrate mRNAs exit the nucleus with a 200+-residue poly(A) tail and are deadenylated to yield heterogeneous polymers of 50-200 adenosine resid ues on any given mRNA. We previously reported that Xenopus albumin mRNA and pre-mRNA have an unusually short, discrete 17-residue poly(A) tail and sho wed that regulation of poly(A) length is controlled independently by two ci s-acting poly(A)-limiting elements (PLE A and PLE B) located in the termina l exon. The present study sought to determine the generality of this regula tory mechanism. Transferrin mRNA also has a discrete <20-nt poly(A) tail, a nd deletion mapping experiments identified an element homologous to the alb umin gene PLE B within the terminal exon of the transferrin gene that confe rred poly(A) length regulation on a globin reporter mRNA. Based on this sim ilarity the PLE B sequence was used in a database search to identify candid ate mRNA targets for regulated polyadenylation. Of the several hundred sequ ences identified in this manner we focused on HIV-EP2/Schnurri-2, a member of a family of genes encoding related zinc finger transcription factors. A striking feature of the PLE-like element in these genes is its location 10- 33 bp upstream of the translation stop codon. We demonstrate that HIV-EP2 m RNA has a <20-nt poly(A) tail, for which the identified PLE-like sequence i s responsible. These results indicate that the presence of a PLE can predic t mRNAs with <20-nt poly(A) tails, and that nuclear regulation of poly(A) t ail length is a feature of many mRNAs.