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Related Concept Videos

RNA-seq03:21

RNA-seq

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RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases. 
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
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RNA Interference01:23

RNA Interference

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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.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
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RNA Structure01:23

RNA Structure

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Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
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Nucleic Acid Structure01:25

Nucleic Acid Structure

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
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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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Nucleic Acids02:43

Nucleic Acids

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Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
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A guide to RNA structure analysis and RNA-targeting methods.

Rodrigo Aguilar1, Constanza Mardones1, Adrian A Moreno2

  • 1Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile.

The FEBS Journal
|December 24, 2024
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Summary
This summary is machine-generated.

RNA therapeutics are promising but challenging due to scarce structural data. This guide reviews RNA structure determination and targeting strategies, advocating for complementary approaches to accelerate drug development.

Keywords:
RNARNA structureRNA targetingnoncoding RNA

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Area of Science:

  • Molecular Biology
  • Drug Discovery
  • Biochemistry

Background:

  • RNAs are emerging as key therapeutic targets, amenable to modulation via small molecules, antisense oligonucleotides, DNAzymes, and CRISPR/Cas13.
  • Unlike protein drug development, RNA-targeting strategies are hindered by limited availability and complexity of comprehensive RNA structure data.
  • Existing RNA structure elucidation methods often reveal dynamic structures rather than static conformations, complicating rational drug design.

Purpose of the Study:

  • To provide an overview of current RNA structure determination methodologies.
  • To explore diverse RNA-targeting strategies, differentiating those that require detailed structural information from those that do not.
  • To guide researchers in selecting appropriate strategies for developing RNA-targeting therapeutics.

Main Methods:

  • Review of established techniques for RNA secondary and three-dimensional structure determination (e.g., X-ray crystallography, cryo-EM, NMR, SHAPE, DMS, bioinformatics).
  • Exploration of RNA-targeting modalities including small molecules, antisense oligonucleotides, DNAzymes, and CRISPR/Cas13.
  • Discussion of sequence-based and phenotypic screening approaches independent of detailed RNA structure.

Main Results:

  • RNA structure determination remains challenging, often yielding information on flexibility and multiple conformations.
  • A spectrum of RNA-targeting strategies exists, varying in their dependence on precise structural data.
  • Sequence-based and phenotypic approaches offer viable alternatives when detailed RNA structures are unavailable or difficult to obtain.

Conclusions:

  • The development of RNA-targeting drugs necessitates a strategic decision regarding the extent of structural information required.
  • Complementary approaches integrating structural data with sequence-based or phenotypic methods can expedite the discovery of novel RNA-targeting therapeutics.
  • Further integration of diverse methodologies will be crucial for advancing RNA-based therapies to combat diseases.