The retroviruses human immunodeficiency virus type 1 and moloney murine leukemia virus adopt radically different strategies to regulate promoter-proximal polyadenylation

Maximal gene expression in retroviruses requires that polyadenylation in th e 5' long terminal repeat (LTR) is suppressed. In human immunodeficiency vi rus type 1 (HIV-1) the promoter-proximal poly(A) site is blocked by interac tion of Ut snRNP with the closely positioned major splice donor site (MSD) 200 nucleotides downstream. Here we investigated whether the same mechanism applies to down-regulate 5' LTR polyadenylation In Moloney murine leukemia virus (MoMLV). Although the same molecular architecture is present in both viruses, the MoMLV poly(A) signal in the 5' LTR is active whether or not t he MSD is mutated. This surprising difference between the two retroviruses is not due to their actual poly(A) signals or MSD sequences, since exchange of either element between the two viral sequences does not alter their abi lity to regulate 5' LTR poly(A) site use. Instead we demonstrate that seque nce between the cap and AAUAAA is required for MSD-dependent poly(A) regula tion in HIV-1, indicating a key role for this part of the LTR in poly(A) si te suppression. We also show that the MoMLV poly(A) signal is an intrinsica lly weak RNA-processing signal. This suggests that in the absence of a poly (A) site suppression mechanism, MoMLV is forced to use a weak poly(A) signa l.