Ending the Message Is Not So Simple Nicholas Proudfoot  Cell  Volume 87, Issue 5, Pages 779-781 (November 1996) DOI: 10.1016/S0092-8674(00)81982-0

Figure 1 Multiple Proteins Mediate Specific Cleavage and Polyadenylation of mRNA 3′ Ends The detailed biochemistry of polyadenylation has been reviewed most recently by Wahle and Keller 1996. The pre-mRNA is shown as a grey line with the indentation indicating the site of cleavage (scissors). The extending poly(A) tail is also included on the diagram with multiple PABII binding. Well defined molecular interactions include the 160kD CPSF subunit with AAUAAA and the 64kD CstF subunit with GU/U (denoted by parallel lines). Also PAP interacts with CPSF by contacting the 160kD subunit and CPSF interacts with CstF by contacts between the 160kD and 77KD subunits. (This diagram was kindly drawn by Tom Furlong). Cell 1996 87, 779-781DOI: (10.1016/S0092-8674(00)81982-0)

Figure 2 Regulated Poly(A) Site Selection Top panel shows 3′ terminal alternate exons (colored boxes) and introns (lines) of the Calcitonin and IgM genes. Splicing patterns and poly(A) signals are indicated, as are activating (+) and inhibiting (-) effects of splice signals or changes in CstF concentration (see text). Middle panel shows diagrams of three regulated mRNA 3′ends. For BPV late, U1A SnRNP interacting with the splice donor element (SD) inhibits polyadenylation. For SV40 late, 3 upstream sequence elements (USE) of the poly(A) site may bind U1A protein as part of U1SnRNP and so enhance polyadenylation by interaction with CPSF. For U1A mRNA, upstream sequences of this poly(A) signal provide binding sites for U1A protein which in turn inhibit polyadenylation thus creating an auto regulatory loop. Bottom panel shows diagrams of two viruses. For HIV-1, the LTRs are blue boxes separated by a line denoting the rest of the viral genome, not drawn to scale. For Adenovirus, the whole virus is depicted as a blue box. As indicated, the major splice donor site of HIV-1 inhibits polyadenylation of 5′LTR transcripts whereas the alternate poly(A) sites of Adenovirus are regulated by decreasing the level of polyadenylation activity during viral infection. (This diagram was kindly drawn by Tom Furlong). Cell 1996 87, 779-781DOI: (10.1016/S0092-8674(00)81982-0)