Endoh Tamaki, Sugimoto Naoki
Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojimaminamimachi, Kobe, 650-0047, Japan.
Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojimaminamimachi, Kobe, 650-0047, Japan.
Sci Rep. 2016 Mar 7;6:22719. doi: 10.1038/srep22719.
G-quadruplexes formed on DNA and RNA can be roadblocks to movement of polymerases and ribosome on template nucleotides. Although folding and unfolding processes of the G-quadruplexes are deliberately studied in vitro, how the mechanical and physical properties of the G-quadruplexes affect intracellular biological systems is still unclear. In this study, mRNAs with G-quadruplex forming sequences located either in the 5' untranslated region (UTR) or in the open reading frame (ORF) were constructed to evaluate positional effects of the G-quadruplex on translation suppression in cells. Periodic fluctuation of translation suppression was observed at every three nucleotides within the ORF but not within the 5' UTR. The results suggested that difference in motion of ribosome at the 5' UTR and the ORF determined the ability of the G-quadruplex structure to act as a roadblock to translation in cells and provided mechanical insights into ribosomal progression to overcome the roadblock.
在DNA和RNA上形成的G-四链体可能会阻碍聚合酶和核糖体在模板核苷酸上的移动。尽管G-四链体的折叠和解折叠过程已在体外进行了深入研究，但G-四链体的机械和物理特性如何影响细胞内生物系统仍不清楚。在本研究中，构建了G-四链体形成序列位于5'非翻译区（UTR）或开放阅读框（ORF）的mRNA，以评估G-四链体对细胞内翻译抑制的位置效应。在ORF内每三个核苷酸处观察到翻译抑制的周期性波动，但在5'UTR内未观察到。结果表明，5'UTR和ORF处核糖体运动的差异决定了G-四链体结构作为细胞内翻译障碍的能力，并为核糖体克服障碍的进展提供了机械学见解。
