THE HIV-1 5'-LTR POLY(A) SITE IS INACTIVATED BY U1 SNRNP INTERACTION WITH THE DOWNSTREAM MAJOR SPLICE DONOR SITE

The inactivity of the 5' long terminal repeat (LTR) poly(A) site immed iately downstream of the cap site maximizes the production of HIV-1 tr anscripts. In this paper, we demonstrate that this inactivity is media ted by the interaction of the U1 snRNP with the major splice donor sit e (MSD), The inhibition of the HIV-1 poly(A) site by U1 snRNP relies o n a series of delicately balanced RNA processing signals, These includ e the poly(A) site, the major splice donor site and the splice accepto r sites. The inherent efficiency of the HIV-1 poly(A) site allows maxi mal activity where there is no donor site (in the 3' LTR) but full inh ibition by the downstream MSD (in the 5' LTR), The MSD must interact e fficiently with U1 snRNP to completely inhibit the 5' LTR poly(A) site , whereas the splice acceptor sites are inefficient, allowing full-len gth genomic RNA production.