Hook Brad A, Goldstrohm Aaron C, Seay Daniel J, Wickens Marvin
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
J Biol Chem. 2007 May 25;282(21):15430-8. doi: 10.1074/jbc.M611253200. Epub 2007 Mar 27.
mRNA stability and translation are regulated by protein repressors that bind 3'-untranslated regions. PUF proteins provide a paradigm for these regulatory molecules: like other repressors, they inhibit translation, enhance mRNA decay, and promote poly(A) removal. Here we show that a single mRNA in Saccharomyces cerevisiae, encoding the HO endonuclease, is regulated by two distinct PUF proteins, Puf4p and Mpt5p. These proteins bind to adjacent sites and can co-occupy the mRNA. Both proteins are required for full repression and deadenylation in vivo; their removal dramatically stabilizes the mRNA. The two proteins act through overlapping but non-identical mechanisms: repression by Puf4p is dependent on deadenylation, whereas repression by Mpt5p can occur through additional mechanisms. Combinatorial action of the two regulatory proteins may allow responses to specific environmental cues and be common in 3'-untranslated region-mediated control.
mRNA稳定性和翻译受结合于3'非翻译区的蛋白质阻遏物调控。PUF蛋白为这些调控分子提供了一个范例：与其他阻遏物一样，它们抑制翻译、增强mRNA降解并促进多聚腺苷酸（poly(A)）去除。在此我们表明，酿酒酵母中一个编码HO核酸内切酶的单一mRNA受两种不同的PUF蛋白Puf4p和Mpt5p调控。这些蛋白结合于相邻位点并可共同占据该mRNA。两种蛋白对于体内的完全阻遏和去腺苷酸化都是必需的；去除它们会显著稳定该mRNA。这两种蛋白通过重叠但不同的机制发挥作用：Puf4p的阻遏依赖于去腺苷酸化，而Mpt5p的阻遏可通过其他机制发生。两种调控蛋白的组合作用可能允许对特定环境信号作出反应，并且在3'非翻译区介导的调控中很常见。
