Control of the polyamine biosynthesis pathway by G(2)-quadruplexes.
Control of the polyamine biosynthesis pathway by G(2)-quadruplexes.
复制标题
G(2)-四链体控制多胺生物合成途径。
作者：
Lightfoot HL;Hagen T;Cléry A;Allain FH;Hall J
G-四链体是RNA和DNA中天然存在的结构。常规RNA G-四链体由于通过短环连接的堆叠平面排列而高度稳定。然而，不规则四链体结构的报道越来越多，最近的全基因组研究表明，它们影响基因表达。我们研究了一组G2基序的UTR的八个基因参与多胺的生物合成，并得出结论，有几个可能形成新的亚稳态RNA G-四链体。我们进行了全面的生物物理特性，它们的属性，比较它们的参考G-四链体。使用细胞分析，与多胺消耗和四链体稳定配体，我们发现了这些图案如何调节和感知多胺水平，在多胺生物合成过程中产生反馈回路。使用高分辨率1H-NMR光谱，我们证明了在AZIN 1 mRNA中的长环四链体与发夹结构共存于盐依赖性平衡中。这项研究扩展了调控G-四链体的库，并展示了它们如何协调一致地控制代谢物的稳态。
G-quadruplexes are naturally-occurring structures found in RNAs and DNAs. Regular RNA G-quadruplexes are highly stable due to stacked planar arrangements connected by short loops. However, reports of irregular quadruplex structures are increasing and recent genome-wide studies suggest that they influence gene expression. We have investigated a grouping of G2-motifs in the UTRs of eight genes involved in polyamine biosynthesis, and concluded that several likely form novel metastable RNA G-quadruplexes. We performed a comprehensive biophysical characterization of their properties, comparing them to a reference G-quadruplex. Using cellular assays, together with polyamine-depleting and quadruplex-stabilizing ligands, we discovered how some of these motifs regulate and sense polyamine levels, creating feedback loops during polyamine biosynthesis. Using high-resolution 1H-NMR spectroscopy, we demonstrated that a long-looped quadruplex in the AZIN1 mRNA co-exists in salt-dependent equilibria with a hairpin structure. This study expands the repertoire of regulatory G-quadruplexes and demonstrates how they act in unison to control metabolite homeostasis.