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Experimental RNAi02:15

Experimental RNAi

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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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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by 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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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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RNA Interference01:23

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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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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Cleavage of MALAT1 RNA by 14-nt sgRNA-guided tRNase ZL.

PloS one·2025
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Updated: Sep 21, 2025

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
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TRUE Gene Silencing.

Masayuki Nashimoto1

  • 1Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.

International Journal of Molecular Sciences
|May 28, 2022
PubMed
Summary

TRUE gene silencing uses small guide RNA (sgRNA) and tRNase ZL to control gene expression. This technology shows potential as novel therapeutics, particularly for multiple myeloma treatment.

Area of Science:

  • Molecular Biology
  • RNA Therapeutics
  • Gene Regulation

Background:

  • TRUE gene silencing is an RNA-mediated technology utilizing tRNase ZL for gene expression control.
  • Cellular small RNAs, including microRNA and tRNA fragments, can function as small guide RNAs (sgRNAs).
  • Human cells harness cytosolic tRNase ZL with small RNAs for gene regulation.

Purpose of the Study:

  • To review the potential of small guide RNA (sgRNA) for TRUE gene silencing as novel therapeutics.
  • To describe the physiology of tRNase ZL, cellular small RNAs, and the mechanism of TRUE gene silencing.
  • To discuss the therapeutic applications of sgRNA, including for multiple myeloma.

Main Methods:

  • Overview of tRNase ZL function in tRNA maturation and its interaction with small RNAs.
Keywords:
RNA therapeuticsTRUE gene silencingmultiple myelomasgRNAtRNase ZLtumor-associated macrophage

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  • Explanation of how artificial sgRNAs direct tRNase ZL to cleave specific target RNAs.
  • Review of TRUE gene silencing applications, including induction of apoptosis in cancer cells.

    • Main Results:

    • TRUE gene silencing enables targeted RNA cleavage at desired sites using sgRNA and tRNase ZL.
    • Demonstration of TRUE gene silencing's efficacy in inducing apoptosis in human cancer cells.
    • Identification of sgRNA's potential as a therapeutic strategy.

    Conclusions:

    • Small guide RNA (sgRNA) holds significant promise as a novel therapeutic agent for gene silencing.
    • TRUE gene silencing technology, leveraging sgRNA and tRNase ZL, offers a versatile platform for therapeutic intervention.
    • Further research into sgRNA-based TRUE gene silencing is warranted for conditions like multiple myeloma.