Gunderson S I, Polycarpou-Schwarz M, Mattaj I W
European Molecular Biology Laboratory, Heidelberg, Germany.
Mol Cell. 1998 Jan;1(2):255-64. doi: 10.1016/s1097-2765(00)80026-x.
It has previously been shown in vivo that bovine papillomavirus represses its late gene expression via a 5' splice site sequence located upstream of the late polyadenylation signal. Here, the mechanism of repression is determined by in vitro analysis. U1 snRNP binding to the 5' splice site results in inhibition of polyadenylation via a direct interaction with poly(A) polymerase (PAP). Although the inhibitory mechanism is similar to that used in U1A autoregulation, U1A within the U1 snRNP does not contribute to PAP inhibition. Instead the U1 70K protein, when bound to U1 snRNA, both interacts with and inhibits PAP. Conservation of the U1 70K inhibitory domains suggests that polyadenylation regulation via PAP inhibition may be more widespread than previously thought.
先前在体内研究表明，牛乳头瘤病毒通过位于晚期聚腺苷酸化信号上游的5'剪接位点序列抑制其晚期基因表达。在此，通过体外分析确定了抑制机制。U1 snRNP与5'剪接位点结合会通过与聚腺苷酸聚合酶（PAP）的直接相互作用抑制聚腺苷酸化。尽管抑制机制与U1A自身调节中使用的机制相似，但U1 snRNP中的U1A对PAP抑制没有作用。相反，当与U1 snRNA结合时，U1 70K蛋白既能与PAP相互作用又能抑制PAP。U1 70K抑制结构域的保守性表明，通过抑制PAP进行的聚腺苷酸化调节可能比以前认为的更为普遍。
