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Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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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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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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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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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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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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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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Related Experiment Video

Updated: Jun 5, 2025

Identification of Circular RNAs using RNA Sequencing
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Identification of Circular RNAs using RNA Sequencing

Published on: November 14, 2019

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Circular RNAs trigger nonsense-mediated mRNA decay.

Sung Ho Boo1, Min-Kyung Shin2, Hyun Jung Hwang1

  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

Molecular Cell
|December 12, 2024
PubMed
Summary
This summary is machine-generated.

Circular RNAs (circRNAs) trigger mRNA degradation via RNA-RNA interactions, initiating circRNA-induced NMD (circNMD). This mechanism offers potential for targeted mRNA downregulation therapies.

Keywords:
EJCRNA-RNA interactionapoptosisback-splicingcircNMDcircular RNAeIF4A3eIF4Enonsense-mediated mRNA decaynuclear cap-binding complex

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Identification of Footprints of RNA:Protein Complexes via RNA Immunoprecipitation in Tandem Followed by Sequencing RIPiT-Seq
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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • Circular RNAs (circRNAs) are RNA molecules with regulatory roles in biological processes.
  • The precise molecular mechanisms governing circRNA function are not fully understood.
  • Investigating circRNA-mediated gene regulation is crucial for understanding cellular processes.

Purpose of the Study:

  • To elucidate the molecular mechanism by which circRNAs regulate gene expression.
  • To identify and characterize circRNA-induced nonsense-mediated mRNA decay (circNMD).
  • To explore the therapeutic potential of circNMD for selective mRNA downregulation.

Main Methods:

  • RNA-RNA interaction analysis between circRNAs and mRNA 3' UTRs.
  • Investigation of exon-junction complex (EJC) positioning and its role in mRNA decay.
  • Transcriptomic analysis to identify circNMD candidates.
  • Experimental validation of circNMD in cellular apoptosis and exogenous expression studies.

Main Results:

  • circRNAs facilitate rapid mRNA degradation through direct RNA-RNA interactions with mRNA 3' UTRs.
  • This interaction recruits EJCs, leading to EJC-dependent nonsense-mediated mRNA decay (NMD), termed circNMD.
  • Hundreds of potential circNMD targets were identified through transcriptomic analysis.
  • circNMD was validated for its role in cellular apoptosis and shown to significantly downregulate target mRNA levels upon exogenous expression.

Conclusions:

  • circRNAs induce mRNA degradation via a novel circNMD pathway.
  • The circNMD mechanism involves RNA-RNA interactions and EJC-mediated NMD.
  • circNMD presents a promising therapeutic strategy for targeted mRNA downregulation.