Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo.,Molecular Cell

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Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo.
Molecular Cell ( IF 14.5 ) Pub Date : 2018-08-23 , DOI: 10.1016/j.molcel.2018.07.028
David J Young ₁ , Desislava S Makeeva ₂ , Fan Zhang ₃ , Aleksandra S Anisimova ₄ , Elena A Stolboushkina ₅ , Fardin Ghobakhlou ₃ , Ivan N Shatsky ₆ , Sergey E Dmitriev ₇ , Alan G Hinnebusch ₃ , Nicholas R Guydosh ₈

Affiliation

Laboratory of Gene Regulation & Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA; Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia; School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.
Laboratory of Gene Regulation & Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.
Institute of Protein Research, Russian Academy of Sciences, Pushchino 142290, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Department of Biochemistry, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia.
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.

The recycling of ribosomal subunits after translation termination is critical for efficient gene expression. Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR) function as 40S recycling factors in vitro, but it is unknown whether they perform this function in vivo. Ribosome profiling of tma deletion strains revealed 80S ribosomes queued behind the stop codon, consistent with a block in 40S recycling. We found that unrecycled ribosomes could reinitiate translation at AUG codons in the 3' UTR, as evidenced by peaks in the footprint data and 3' UTR reporter analysis. In vitro translation experiments using reporter mRNAs containing upstream open reading frames (uORFs) further established that reinitiation increased in the absence of these proteins. In some cases, 40S ribosomes appeared to rejoin with 60S subunits and undergo an 80S reinitiation process in 3' UTRs. These results support a crucial role for Tma64, Tma20, and Tma22 in recycling 40S ribosomal subunits at stop codons and translation reinitiation.

中文翻译：

Tma64 / eIF2D，Tma20 / MCT-1和Tma22 / DENR在体内回收终止后的40S亚基。

翻译终止后核糖体亚基的回收对于有效的基因表达至关重要。Tma64（eIF2D），Tma20（MCT-1）和Tma22（DENR）在体外起40S回收因子的作用，但尚不清楚它们是否在体内发挥此功能。tma缺失菌株的核糖体分析显示，80S核糖体排在终止密码子后面，与40S回收中的一个阻滞一致。我们发现未回收的核糖体可以在3'UTR中的AUG密码子处重新启动翻译，这是由足迹数据和3'UTR报告基因分析的峰值所证明的。使用含有上游开放阅读框（uORF）的报告基因mRNA进行的体外翻译实验进一步确定，在缺少这些蛋白质的情况下，重新初始化会增加。在某些情况下，40S核糖体似乎与60S亚基重新结合，并在3'UTR中经历80S重新初始化过程。这些结果支持Tma64，Tma20和Tma22在终止密码子和翻译重新起始中回收40S核糖体亚基中的关键作用。

更新日期：2018-08-23

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