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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...
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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 the pre-miRNA...
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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
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Related Experiment Video

Updated: May 27, 2025

Identification of Circular RNAs using RNA Sequencing
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Development and characterization of a miRNA-responsive circular RNA expression system with cell type specificity.

Yu Ma1, Yuqiao Mao2, Shirui Luo2

  • 1Suzhou Abogen Biosciences Company, Suzhou 215123, China.

Molecular Therapy. Nucleic Acids
|February 19, 2025
PubMed
Summary
This summary is machine-generated.

This study demonstrates that circular RNAs (circRNAs) can be engineered to express genes in response to specific microRNAs (miRNAs). This novel approach enables targeted gene expression, advancing therapeutic applications for circRNAs.

Keywords:
HCVMT: RNA and epigenetic editing Special Issuecell-type-specific expressioncircRNAmicroRNAtranslation activation

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Area of Science:

  • Molecular Biology
  • Gene Therapy
  • RNA Therapeutics

Background:

  • MicroRNAs (miRNAs) typically degrade messenger RNAs (mRNAs).
  • However, miRNAs can enhance viral RNA expression via internal ribosome entry sites (IRES).
  • This interaction suggests potential for miRNA-mediated control of RNA expression.

Purpose of the Study:

  • To develop a novel strategy for inducible and tissue-specific gene expression using circular RNAs (circRNAs).
  • To investigate the potential of using miRNA binding sites within circRNA IRES elements for translational control.
  • To explore the therapeutic applications of miRNA-regulated circRNAs.

Main Methods:

  • Constructed circRNAs incorporating the hepatitis C virus (HCV) 5' UTR with miR-122 binding sites as an IRES.
  • Transfected cells with engineered circRNAs to assess miRNA-inducible gene expression.
  • Utilized alternative miRNA binding sites to demonstrate broad applicability.
  • Administered lipid nanoparticle-formulated circRNAs (circRNA-LNPs) intravenously in mouse models.

Main Results:

  • Engineered circRNAs demonstrated specific, inducible gene expression in response to miR-122.
  • Substituting miR-122 sites with other miRNA binding sites enabled corresponding miRNA-mediated translational activation.
  • In vivo studies showed enhanced tissue-specific expression of circRNA-LNPs with functional miRNA binding sites compared to mutated controls.

Conclusions:

  • Introduced a novel method for regulating circRNA expression using miRNA targeting.
  • Demonstrated the potential for tissue-specific gene expression control via engineered circRNAs.
  • This strategy holds promise for advancing gene therapy and developing precise therapeutic interventions.