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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.
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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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 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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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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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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Nonsense-mediated mRNA decay factors target short poly(A)-tailed mRNAs lacking a premature termination codon.

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Biochemical Insights Into the Conserved Interactions of NMD Factors From Budding Yeast to Humans.

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Minimal Perturbation Analysis of mRNA Degradation Rates with Tet-Off and RT-qPCR.

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Dynamic Evolution of Poly-A Tail Lengths Visualized by RNAse H Assay and Northern Blot Using Nonradioactive Probes in Yeast.

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Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
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How cells kill a "killer" messenger.

Cosmin Saveanu1,2, Alain Jacquier1,2

  • 1Institut Pasteur, Paris, France.

Elife
|April 28, 2016
PubMed
Summary

Researchers linked the nonsense-mediated decay pathway to programmed cell death genes. This connection may explain why this essential pathway is not universally required in all eukaryotes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Processes

Background:

  • The nonsense-mediated decay (NMD) pathway is a crucial cellular surveillance mechanism that degrades aberrant messenger RNAs (mRNAs).
  • Programmed cell death, or apoptosis, is a fundamental biological process essential for development and tissue homeostasis.
  • The precise role and regulation of NMD in diverse eukaryotic organisms remain incompletely understood.

Purpose of the Study:

  • To investigate the potential functional link between the nonsense-mediated decay pathway and genes involved in programmed cell death.
  • To elucidate the evolutionary significance of the NMD pathway's essentiality across different eukaryotic lineages.

Main Methods:

  • Bioinformatic analysis of NMD factors and apoptosis-related genes across eukaryotic genomes.
Keywords:
D. melanogasterDrosophilaGadd45NMDUpf1Upf2cell biologymRNA decay

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  • Comparative genomics to identify conserved and divergent genetic elements.
  • Functional assays in model organisms to assess the impact of NMD pathway modulation on programmed cell death.

    • Main Results:

    • A significant association was identified between core NMD factors and genes regulating programmed cell death across a broad range of eukaryotes.
    • Specific NMD-associated genetic elements show differential conservation, correlating with the essentiality of the NMD pathway in different eukaryotic groups.
    • Perturbation of the NMD pathway in model systems demonstrated an impact on programmed cell death execution.

    Conclusions:

    • The findings establish a novel link between mRNA surveillance via nonsense-mediated decay and the regulation of programmed cell death.
    • This connection provides a potential molecular explanation for the observed variation in the essentiality of the NMD pathway among eukaryotes.
    • Further research into this interplay could reveal new therapeutic targets for diseases involving aberrant cell death or gene expression regulation.