A Potassium Ion-Dependent RNA Structural Switch Regulates Human Pre-miRNA 92b Maturation
A Potassium Ion-Dependent RNA Structural Switch Regulates Human Pre-miRNA 92b Maturation
复制标题
DOI：
10.1016/j.chembiol.2014.12.013
复制
发表时间：
2015-02-19
影响因子：
--
通讯作者：
Basu, Soumitra
中科院分区：
文献类型：
--
作者：
Arachchilage, Gayan Mirihana;Dassanayake, Arosha C.;Basu, Soumitra
MicroRNAs （miRNAs）是一组重要的寡核苷酸序列，其生物发生涉及dicer介导的裂解作为关键步骤。Dicer切割前体miRNA （pre-miRNA）茎环结构以产生成熟的miRNA。通过生物信息学分析，我们发现在大约16%的pre- mirna中存在假定的g -四重体（GQ）形成序列。我们报道了在临床上重要的人类premiRNA 92b中存在GQ作为标准茎环结构的替代方案。GQ的形成导致茎环结构的解绕，从而在体外和体内对dicer介导的裂解产生抗性。GQ和茎环结构之间潜在的K+离子依赖平衡能够调节dicer介导的pre-miRNA 92b成熟，从而影响靶基因沉默。这些发现揭示了前mirna成熟调控的新机制，尽管是在RNA结构水平上。
MicroRNAs (miRNAs) are an important set of oligonucleotide sequences with a biogenesis that involves Dicer-mediated cleavage as a critical step. Dicer cleaves the precursor miRNA (pre-miRNA) stem-loop structure to produce the mature miRNA. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ)-forming sequences in about 16% of pre-miRNAs. We report the existence of a GQ as an alternative to the canonical stem-loop structure in the clinically important human premiRNA 92b. GQ formation led to unwinding of the stem-loop structure imparting resistance to Dicer-mediated cleavage both in vitro and in vivo. A potential K+ ion-dependent equilibrium between GQ and the stem-loop structure has the ability to regulate the Dicer-mediated maturation of pre-miRNA 92b, which consequently affects target gene silencing. These findings unravel a new mechanism of regulation in pre-miRNA maturation, albeit at the RNA structure level.