Richards Jamie, Mehta Preeti, Karzai A Wall
Department of Biochemistry and Cell Biology, Center for Infectious Diseases of Stony Brook University, Stony Brook, NY 11794, USA.
Mol Microbiol. 2006 Dec;62(6):1700-12. doi: 10.1111/j.1365-2958.2006.05472.x.
The SmpB-tmRNA-mediated trans-translation system has two well-established activities: rescuing ribosomes stalled on aberrant mRNAs and marking the associated protein fragments for proteolysis. Although the causative non-stop mRNAs are known to be degraded, little is known about the enabling mechanism or the RNases involved in their disposal. We report that Escherichia coli has an enabling mechanism that requires RNase R activity and is dependent on the presence of SmpB protein and tmRNA, suggesting a requirement for active transtranslation in facilitating RNase R engagement and promoting non-stop mRNA decay. Interestingly, this selective transcript degradation by RNase R targets aberrant (non-stop and multiple-rare-codon containing) mRNAs and does not affect the decay of related messages containing in-frame stop codons. Most surprisingly, RNase II and PNPase do not play a significant role in tmRNA-facilitated disposal of aberrant mRNAs. These findings demonstrate that RNase R is a crucial component of the trans-translation-mediated non-stop mRNA decay process, thus providing a requisite activity well suited to complement the ribosome rescue and protein tagging functions of this unique quality control system.
SmpB-tmRNA介导的反式翻译系统具有两个已被充分证实的功能：拯救停滞在异常mRNA上的核糖体，并标记相关蛋白质片段以便进行蛋白水解。尽管已知导致无义的mRNA会被降解，但对于其降解机制或参与降解的核糖核酸酶却知之甚少。我们报告称，大肠杆菌具有一种依赖核糖核酸酶R活性的降解机制，且该机制依赖于SmpB蛋白和tmRNA的存在，这表明在促进核糖核酸酶R参与和推动无义mRNA降解过程中，需要有活性的反式翻译。有趣的是，核糖核酸酶R介导的这种选择性转录本降解作用针对的是异常（无义及含有多个稀有密码子）mRNA，而不影响含有框内终止密码子的相关mRNA的降解。最令人惊讶的是，核糖核酸酶II和多核苷酸磷酸化酶在tmRNA促进的异常mRNA降解过程中并不起重要作用。这些发现表明，核糖核酸酶R是反式翻译介导的无义mRNA降解过程的关键组成部分，从而提供了一种必要的活性，非常适合补充这个独特质量控制系统的核糖体拯救和蛋白质标记功能。
