Related Experiment Video
Updated: Sep 14, 2025
06:48
A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
Published on: June 16, 2022
2.1K
MicroRNA-responsive ON-OFF hybrid mRNA switch for precise protein expression control.
Kaito Masaki1,2, Yoshihiko Fujita1, Hirohide Saito1,3
1Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Molecular Therapy. Nucleic Acids
|July 21, 2025
Summary
Scientists developed a novel microRNA (miRNA)-sensing hybrid messenger RNA (mRNA) switch. This ON-OFF technology precisely controls protein expression in specific cells, advancing mRNA therapeutics.
Area of Science:
- Biotechnology
- Molecular Biology
- Therapeutics Development
Background:
- Messenger RNA (mRNA) technology shows promise for next-generation therapeutics.
- Controlling mRNA translation for cell- and tissue-specific protein expression is a significant challenge.
Purpose of the Study:
- To develop an advanced mRNA switch for precise translational regulation.
- To engineer a hybrid mRNA switch capable of sensing specific microRNAs (miRNAs) for targeted protein expression.
Main Methods:
- Designed a hybrid mRNA switch integrating an ON-type (miRNA-activated) and an OFF-type (miRNA-repressed) system.
- Investigated optimal module sequences following the poly(A)-tail for the ON-type switch.
- Validated the switch's performance in vitro human cell cultures and in vivo mouse models.
Main Results:
- The hybrid mRNA switch demonstrated reduced expression leakage in non-target cells.
- Achieved enhanced ON/OFF selectivity for protein expression.
- Confirmed appropriate translational activation in response to target cell-specific miRNAs.
Conclusions:
- The developed ON-OFF hybrid mRNA switch enables selective protein expression in designated cells.
- This technology represents a significant advancement for the next generation of mRNA therapeutics.
- Offers enhanced precision in translational control for therapeutic applications.
Keywords:
MT: Oligonucleotides: Therapies and ApplicationsRNA engineeringRNA switchmicroRNAsynthetic biologysynthetic mRNAtranslation regulationMore Related Videos
09:17Combining Optogenetics with Artificial microRNAs to Characterize the Effects of Gene Knockdown on Presynaptic Function within Intact Neuronal Circuits
Published on: March 14, 2018
10.3K
07:19Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
Published on: September 28, 2011
36.3K
Related Concept Videos
01:22MicroRNAs
21.8K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.8K
01:56Riboswitches
8.5K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.5K
02:15Experimental RNAi
6.3K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.3K
01:23Regulation of Expression at Multiple Steps
1.0K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.0K
01:23Transcriptional Regulation: Riboswitches
116
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
116
01:29Translational Regulation
99
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
99