DEAD盒蛋白Dhh1p通过监测密码子优化来耦合mRNA衰变与翻译。
The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality.
作者信息
Radhakrishnan Aditya, Chen Ying-Hsin, Martin Sophie, Alhusaini Najwa, Green Rachel, Coller Jeff
机构信息
Program in Molecular Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
出版信息
Cell. 2016 Sep 22;167(1):122-132.e9. doi: 10.1016/j.cell.2016.08.053. Epub 2016 Sep 15.
A major determinant of mRNA half-life is the codon-dependent rate of translational elongation. How the processes of translational elongation and mRNA decay communicate is unclear. Here, we establish that the DEAD-box protein Dhh1p is a sensor of codon optimality that targets an mRNA for decay. First, we find mRNAs whose translation elongation rate is slowed by inclusion of non-optimal codons are specifically degraded in a Dhh1p-dependent manner. Biochemical experiments show Dhh1p is preferentially associated with mRNAs with suboptimal codon choice. We find these effects on mRNA decay are sensitive to the number of slow-moving ribosomes on an mRNA. Moreover, we find Dhh1p overexpression leads to the accumulation of ribosomes specifically on mRNAs (and even codons) of low codon optimality. Lastly, Dhh1p physically interacts with ribosomes in vivo. Together, these data argue that Dhh1p is a sensor for ribosome speed, targeting an mRNA for repression and subsequent decay.
mRNA半衰期的一个主要决定因素是密码子依赖的翻译延伸速率。翻译延伸过程与mRNA降解过程如何相互作用尚不清楚。在此，我们证实DEAD-box蛋白Dhh1p是一种密码子最优性传感器，可靶向mRNA进行降解。首先，我们发现那些因包含非最优密码子而导致翻译延伸速率减慢的mRNA会以依赖Dhh1p的方式被特异性降解。生化实验表明，Dhh1p优先与密码子选择次优的mRNA结合。我们发现这些对mRNA降解的影响对mRNA上慢速移动核糖体的数量敏感。此外，我们发现Dhh1p的过表达会导致核糖体特异性地在密码子最优性低的mRNA（甚至密码子）上积累。最后，Dhh1p在体内与核糖体发生物理相互作用。总之，这些数据表明Dhh1p是核糖体速度的传感器，靶向mRNA进行抑制及随后的降解。
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