Vilela C, Linz B, Rodrigues-Pousada C, McCarthy J E
Posttranscriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, Manchester M60 1QD, UK.
Nucleic Acids Res. 1998 Mar 1;26(5):1150-9. doi: 10.1093/nar/26.5.1150.
Two forms of post-transcriptional control direct differential expression of the Saccharomyces cerevisiae genes encoding the AP1-like transcription factors Yap1p and Yap2p. The mRNAs of these genes contain respectively one (YAP1 uORF) and two (YAP2 uORF1 and uORF2) upstream open reading frames. uORF-mediated modulation of post-termination events on the 5'-untranslated region (5'-UTR) directs differential control not only of translation but also of mRNA decay. Translational control is defined by two types of uORF function. The YAP1 -type uORF allows scanning 40S subunits to proceed via leaky scanning and re-initiation to the major ORF, whereas the YAP2 -type acts to block ribosomal scanning by promoting efficient termination. At the same time, the YAP2 uORFs define a new type of mRNA destabilizing element. Both post-termination ribosome scanning behaviour and mRNA decay are influenced by the coding sequence and mRNA context of the respective uORFs, including downstream elements. Our data indicate that release of post-termination ribosomes promotes largely upf -independent accelerated decay. It follows that translational termination on the 5'-UTR of a mature, non-aberrant yeast mRNA can trigger destabilization via a different pathway to that used to rid the cell of mRNAs containing premature stop codons. This route of control of non-aberrant mRNA decay influences the stress response in yeast. It is also potentially relevant to expression of the sizable number of eukaryotic mRNAs that are now recognized to contain uORFs.
转录后调控的两种形式直接指导酿酒酵母中编码AP1样转录因子Yap1p和Yap2p的基因的差异表达。这些基因的mRNA分别含有一个（YAP1上游开放阅读框）和两个（YAP2上游开放阅读框1和上游开放阅读框2）上游开放阅读框。上游开放阅读框介导的对5'非翻译区（5'-UTR）终止后事件的调控不仅指导翻译的差异控制，还指导mRNA降解的差异控制。翻译控制由两种类型的上游开放阅读框功能定义。YAP1型上游开放阅读框允许扫描的40S亚基通过漏扫描和重新起始进入主要开放阅读框，而YAP2型则通过促进有效终止来阻止核糖体扫描。同时，YAP2上游开放阅读框定义了一种新型的mRNA不稳定元件。终止后核糖体扫描行为和mRNA降解均受各自上游开放阅读框的编码序列和mRNA背景的影响，包括下游元件。我们的数据表明，终止后核糖体的释放很大程度上促进了不依赖于upf的加速降解。因此，成熟、无异常的酵母mRNA的5'-UTR上的翻译终止可以通过与用于清除含有提前终止密码子的mRNA的途径不同的途径触发不稳定。这种对无异常mRNA降解的控制途径影响酵母中的应激反应。它也可能与现在被认为含有上游开放阅读框的大量真核mRNA的表达有关。
