Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Functional Genomics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
FEBS Lett. 2020 Dec;594(24):4357-4369. doi: 10.1002/1873-3468.13928. Epub 2020 Oct 4.
Chemically modified mRNAs are extensively studied with a view toward their clinical application. In particular, long noncoding RNAs (lncRNAs) containing SINE elements, which enhance the translation of their target mRNAs (i.e., SINEUPs), have potential as RNA therapies for various diseases, such as haploinsufficiencies. To establish a SINEUP-based system for efficient protein expression, we directly transfected chemically modified in vitro transcribed (mIVT) SINEUP RNAs to examine their effects on target mRNA translation. mIVT SINEUP RNAs enhanced translation of EGFP mRNA and endogenous target Sox9 mRNA in both cultured cells and a cell-free translation system. Our findings reveal the functional role of RNA modifications in SINEUPs and suggest several broad clinical applications of such an RNA regulatory system.
化学修饰的 mRNA 正在被广泛研究，以期将其应用于临床。特别是，含有 SINE 元件的长非编码 RNA（lncRNA）能够增强其靶 mRNA 的翻译（即 SINEUPs），它们有可能成为治疗各种疾病的 RNA 疗法，例如单倍体不足。为了建立基于 SINEUP 的高效蛋白质表达系统，我们直接转染化学修饰的体外转录（mIVT）SINEUP RNA，以研究它们对靶 mRNA 翻译的影响。mIVT SINEUP RNA 增强了培养细胞和无细胞翻译系统中 EGFP mRNA 和内源性靶 Sox9 mRNA 的翻译。我们的研究结果揭示了 RNA 修饰在 SINEUPs 中的功能作用，并为这种 RNA 调控系统的几个广泛的临床应用提供了线索。
