Spatiotemporal control of microRNA function using light-activated antagomirs.
Spatiotemporal control of microRNA function using light-activated antagomirs.
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DOI：
10.1039/c2mb25175b
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发表时间：
2012-11
影响因子：
--
通讯作者：
Deiters A
中科院分区：
文献类型：
--
作者：
Connelly CM;Uprety R;Hemphill J;Deiters A
MicroRNA（miRNAs）是一类小的非编码RNA，具有转录后基因调控功能，参与胚胎发育、细胞分化、凋亡和增殖等多种生物学过程。某些miRNA表达的变化与多种人类疾病（尤其是癌症）有关，miRNA靶点的多样性表明它们参与了各种细胞网络。已经开发了几种工具来控制单个miRNA的功能，并已被应用于研究它们的生物起源，生物学作用和治疗潜力;然而，常用的方法缺乏精确的控制水平，无法以高的空间和时间分辨率研究miRNA的功能。成熟miR-122和miR-21的光激活miRNA引物通过在所选核苷酸的碱基上位点特异性地安装笼化基团来开发。笼状核苷酸的安装导致完全抑制Eschomir-miRNA杂交，从而使Eschomir功能失活。通过短暂的UV照射，在解除老化后，笼化的黑腹鼠的miRNA抑制活性完全恢复。将合成的miRNAs应用于哺乳动物细胞中miRNA功能的光化学调控。此外，在哺乳动物细胞中通过局部UV暴露获得了对Eschomir活性的空间控制。所提出的方法能够使用UV照射以前所未有的空间和时间分辨率精确调节miRNA功能和miRNA网络，并且可以扩展到任何感兴趣的miRNA。
MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators and have been shown to regulate many biological processes including embryonal development, cell differentiation, apoptosis, and proliferation. Variations in the expression of certain miRNAs have been linked to a wide range of human diseases – especially cancer – and the diversity of miRNA targets suggests that they are involved in various cellular networks. Several tools have been developed to control the function of individual miRNAs and have been applied to study their biogenesis, biological role, and therapeutic potential; however, common methods lack a precise level of control that allows for the study of miRNA function with high spatial and temporal resolution. Light-activated miRNA antagomirs for mature miR-122 and miR-21 were developed through the site-specific installation of caging groups on the bases of selected nucleotides. Installation of caged nucleotides led to complete inhibition of the antagomir-miRNA hybridization and thus inactivation of antagomir function. The miRNA-inhibitory activity of the caged antagomirs was fully restored upon decaging through a brief UV irradiation. The synthesized antagomirs were applied to the photochemical regulation of miRNA function in mammalian cells. Moreover, spatial control over antagomir activity was obtained in mammalian cells through localized UV exposure. The presented approach enables the precise regulation of miRNA function and miRNA networks with unprecedented spatial and temporal resolution using UV irradiation and can be extended to any miRNA of interest.
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影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
影响因子：
48
作者：
Ebert, Margaret S.;Neilson, Joel R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
DOI：
10.1126/science.1215691
发表时间：
2012-04-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Djuranovic S;Nahvi A;Green R
通讯作者：
Green R
影响因子：
--
作者：
Iguchi, Haruhisa;Kosaka, Nobuyoshi;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro