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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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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.
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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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Types of RNA01:20

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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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Nuclear Export of mRNA02:31

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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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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mRNA Stability and Gene Expression02:51

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Related Experiment Video

Updated: Jun 16, 2025

Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes
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Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes

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Small Molecule RNA Degraders.

Javier Bonet-Aleta1, Tomoaki Maehara1, Benjamin A Craig1

  • 1Yusuf Hamied Department of Chemistry, University of Cambridge, CB2 1EW, Cambridge, United Kingdom.

Angewandte Chemie (International Ed. in English)
|August 20, 2024
PubMed
Summary
This summary is machine-generated.

Reprogramming simple RNA binders into potent RNA degraders is crucial for advancing RNA-targeted therapies. This review explores strategies to convert RNA binders into effective degraders, enhancing therapeutic potential.

Keywords:
RNAdegradationproximity-inducedsmall-moleculetherapy

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Area of Science:

  • Molecular Biology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • RNA is vital in biological processes and disease, making it a therapeutic target.
  • Current RNA-targeting strategies often face limitations due to non-functional RNA interactions.
  • Small molecule binding to RNA does not always translate to clinical efficacy.

Purpose of the Study:

  • To review strategies for converting small molecule RNA binders into RNA degraders.
  • To explore mechanisms for enhancing RNA-targeting therapeutic efficacy.
  • To provide insights into advancing RNA-targeted drug discovery.

Main Methods:

  • Review of literature on reprogramming RNA binders into degraders.
  • Categorization of degradation mechanisms: endogenous enzyme-mediated (RIBOTACs) and autonomous degradation.
  • Analysis of strategies involving functional group linkage to small molecule binders.

Main Results:

  • Small molecule binders can be engineered into RNA degraders.
  • Two main classes of RNA degradation strategies are identified: RIBOTACs and autonomous degraders.
  • Successful reprogramming enhances the therapeutic potential of RNA-targeting agents.

Conclusions:

  • Converting RNA binders to degraders offers a promising therapeutic strategy.
  • Engineered RNA degraders can overcome limitations of simple binders.
  • Further development in this area holds significant potential for treating diseases.