Mann K P, Weiss E A, Nevins J R
Section of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina.
Mol Cell Biol. 1993 Apr;13(4):2411-9. doi: 10.1128/mcb.13.4.2411-2419.1993.
The recognition and processing of a pre-mRNA to create a poly(A) addition site, a necessary step in mRNA biogenesis, can also be a regulatory event in instances in which the frequency of use of a poly(A) site varies. One such case is found during the course of an adenovirus infection. Five poly(A) sites are utilized within the major late transcription unit to produce more than 20 distinct mRNAs during the late phase of infection. The proximal half of the major late transcription unit is also expressed during the early phase of a viral infection. During this early phase of expression, the L1 poly(A) site is used three times more frequently than the L3 poly(A) site. In contrast, the L3 site is used three times more frequently than the L1 site during the late phase of infection. Recent experiments have suggested that the recognition of the poly(A) site GU-rich downstream element by the CF1 processing factor may be a rate-determining step in poly(A) site selection. We demonstrate that the interaction of CF1 with the L1 poly(A) site is less stable than the interaction of CF1 with the L3 poly(A) site. We also find that there is a substantial decrease in the level of CF1 activity when an adenovirus infection proceeds to the late phase. We suggest that this reduction in CF1 activity, coupled with the relative instability of the interaction with the L1 poly(A) site, contributes to the reduced use of the L1 poly(A) site during the late stage of an adenovirus infection.
前体mRNA的识别与加工以产生聚腺苷酸（poly(A)）添加位点，这是mRNA生物合成中的必要步骤，在poly(A)位点使用频率发生变化的情况下，也可能是一个调控事件。在腺病毒感染过程中就发现了这样一个例子。在主要晚期转录单元内利用五个poly(A)位点，在感染后期产生20多种不同的mRNA。主要晚期转录单元的近端一半在病毒感染的早期阶段也会表达。在这个早期表达阶段，L1 poly(A)位点的使用频率比L3 poly(A)位点高两倍。相比之下，在感染后期，L3位点的使用频率比L1位点高两倍。最近的实验表明，CF1加工因子对富含GU的poly(A)位点下游元件的识别可能是poly(A)位点选择中的限速步骤。我们证明，CF1与L1 poly(A)位点的相互作用比CF1与L3 poly(A)位点的相互作用更不稳定。我们还发现，当腺病毒感染进入后期时，CF1活性水平会大幅下降。我们认为，CF1活性的这种降低，加上与L1 poly(A)位点相互作用的相对不稳定性，导致腺病毒感染后期L1 poly(A)位点的使用减少。
