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. 2020 Dec;594(24):4357-4369.
doi: 10.1002/1873-3468.13928. Epub 2020 Oct 4.

Synthetic in vitro transcribed lncRNAs (SINEUPs) with chemical modifications enhance target mRNA translation

Naoko Toki  1   2 , Hazuki Takahashi  1   2 , Silvia Zucchelli  3 , Stefano Gustincich  4   5 , Piero Carninci  1   2
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Free article

Synthetic in vitro transcribed lncRNAs (SINEUPs) with chemical modifications enhance target mRNA translation

Naoko Toki et al. FEBS Lett. 2020 Dec.
Free article

Abstract

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.

Keywords: RNA modification; enhancement of endogenous target mRNA translation; in vitro transcribed RNA; nucleic acid-based therapeutics.

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