Are U4 small nuclear ribonucleoproteins involved in polyadenylation?

The mechanism whereby eukaryotic pre-messenger RNAs are polyadenylated is unknown. Most models for polyadenylation invoke cleavage of precursor transcripts at the site of poly(A) addition followed by polymerization of A residues by poly(A) polymerase. Analysis of the sequences surrounding poly(A) addition sites has identified the consensus recognition sequence element AAUAAA as necessary but not sufficient for polyadenylation. A second recognition sequence element CACUG , was observed by Benoit et al. to be adjacent to the site of poly(A) addition in several sequenced RNAs. Here, we analyse 61 vertebrate poly(A) addition sequences, define a more extensive recognition sequence for polyadenylation than previously recognized and suggest how the site of poly(A) addition may be chosen. Furthermore, we find that the defined recognition sequence has elements which are complementary to regions within the small nuclear RNA U4, suggesting that U4 small nuclear ribonucleoproteins (snRNPs) may mediate polyadenylation in a fashion similar to the role of U1 snRNPs in splicing. The model invokes hybridization of U4 RNA to AAUAAA recognition elements as related to primary site selection, and hybridization to CAYUG recognition elements as related to cleavage site selection.