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Related Concept Videos

Types of RNA01:23

Types of RNA

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Overview
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 the regulation of 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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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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Experimental RNAi02:15

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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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siRNA - Small Interfering RNAs02:30

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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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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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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes
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Programming inactive RNA-binding small molecules into bioactive degraders.

Yuquan Tong1, Yeongju Lee1, Xiaohui Liu1

  • 1Department of Chemistry, The Scripps Research Institute & The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.

Nature
|May 24, 2023
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Summary
This summary is machine-generated.

Researchers explored how small molecules interact with RNA, finding many bind weakly. They developed a new method to degrade target RNA using these binders, successfully targeting disease-related microRNA-155 and mRNAs.

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Area of Science:

  • Molecular Biology
  • Medicinal Chemistry
  • RNA Therapeutics

Background:

  • Small molecule binding to RNA is challenging for achieving biological activity.
  • Understanding RNA-small molecule interactions is crucial for drug discovery.

Purpose of the Study:

  • To investigate molecular recognition patterns between small molecules and 3D RNA structures.
  • To explore strategies for modulating RNA biology using small molecules.
  • To develop RNA-targeted degraders for therapeutic applications.

Main Methods:

  • Studied interactions between a natural-product-inspired small molecule collection and folded RNA structures.
  • Mapped RNA-small molecule interaction landscapes across the human transcriptome.
  • Designed ribonuclease-targeting chimeras to induce RNA cleavage.
  • Validated degraders for precursor microRNA-155, JUN mRNA, and MYC mRNA.

Main Results:

  • Identified structure-activity relationships for RNA-small molecule interactions.
  • Found most interactions were predicted to be biologically inert due to binding location.
  • Demonstrated that inactive binders can be converted into potent RNA degraders.
  • Successfully designed selective degraders for specific RNA targets.

Conclusions:

  • Small molecule-RNA interactions can be leveraged for targeted RNA degradation.
  • Ribonuclease-targeting chimeras offer a strategy to convert weak binders into potent modulators of RNA function.
  • This approach holds promise for developing novel RNA-targeted therapeutics.