Back

Nitro Reduction-Based RNA Control and Ultrafast Release

Zhao, Y.; Zhang, S.; Guo, J.; Kha, T.-K.; Chen, S.; Hu, C.; ZHU, R.-Y.

2026-03-01 biochemistry
10.64898/2026.02.28.708682 bioRxiv
Show abstract

RNA protection and controlled release are critical for both fundamental research and therapeutic applications, yet the development of simple, efficient, and reversible post-synthetic RNA modification strategies remains a significant challenge. Here, we introduce a straight forward approach based on ribose 2'-hydroxyl acylation with a nitro-functionalized carbamate, which acts as a redox-responsive center. This modification selectively inhibits native RNA function while remaining inert to endogenous biogenic reductants and common reducing agents used in biological assays. Upon treatment with low millimolar concentrations of the THDB- BIPY reducing pair, RNA function is rapidly restored on a minute timescale. This methodology is broadly applicable across diverse RNA classes and functional contexts, including synthetic RNA oligomers, fluorogenic RNA aptamers, single-guide RNAs in CRISPR-Cas9 gene-editing systems, and mRNAs in living cells for translation control and RNAi-mediated gene silencing. These results demonstrate the general utility of this approach as a chemically controllable functional switch, providing a versatile toolkit for temporal regulation of RNA activity in both research and biotechnological applications.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
Journal of the American Chemical Society
199 papers in training set
Top 0.2%
18.7%
2
Nature Communications
4913 papers in training set
Top 9%
14.8%
3
Nature Chemical Biology
104 papers in training set
Top 0.1%
10.1%
4
Nucleic Acids Research
1128 papers in training set
Top 2%
9.2%
50% of probability mass above
5
Nature Chemistry
34 papers in training set
Top 0.1%
7.2%
6
Angewandte Chemie International Edition
81 papers in training set
Top 0.3%
7.2%
7
ACS Central Science
66 papers in training set
Top 0.1%
6.8%
8
ACS Chemical Biology
150 papers in training set
Top 0.7%
2.4%
9
Advanced Science
249 papers in training set
Top 11%
1.7%
10
Proceedings of the National Academy of Sciences
2130 papers in training set
Top 32%
1.7%
11
Nature Biotechnology
147 papers in training set
Top 4%
1.7%
12
Nature Nanotechnology
30 papers in training set
Top 0.6%
1.7%
13
Cell Chemical Biology
81 papers in training set
Top 2%
1.2%
14
Science
429 papers in training set
Top 18%
0.9%
15
ChemBioChem
50 papers in training set
Top 1.0%
0.9%
16
JACS Au
35 papers in training set
Top 0.9%
0.8%
17
ACS Nano
99 papers in training set
Top 4%
0.7%
18
RSC Chemical Biology
32 papers in training set
Top 0.5%
0.7%
19
Chemical Science
71 papers in training set
Top 2%
0.6%
20
Advanced Materials
53 papers in training set
Top 2%
0.5%
21
Angewandte Chemie
12 papers in training set
Top 0.5%
0.5%
22
eLife
5422 papers in training set
Top 64%
0.5%