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Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

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Related Experiment Video

Updated: Jul 4, 2026

High-throughput Screening for Protein-based Inheritance in S. cerevisiae
08:12

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Depleting prion protein using splice-switching small molecules.

Bo Liu, Benjamin Fair, Zhiling Kuang

    Biorxiv : the Preprint Server for Biology
    |July 3, 2026
    PubMed
    Summary
    This summary is machine-generated.

    Researchers developed a novel small molecule, CP3, that reduces prion protein (PrP) by targeting PRNP gene splicing. This approach, dependent on Luc7L, significantly lowered PrP in mice, offering a new therapeutic strategy for prion diseases.

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    Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
    12:57

    Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

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    Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts
    07:02

    Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

    Published on: May 11, 2018

    Area of Science:

    • Neuroscience
    • Molecular Biology
    • Pharmacology

    Background:

    • Prion diseases are fatal neurodegenerative disorders caused by misfolded prion protein (PrP).
    • Lowering cellular PrP levels is a key therapeutic goal for treating these conditions.

    Purpose of the Study:

    • To develop a small-molecule strategy for reducing PrP by modulating PRNP gene pre-mRNA splicing.
    • To investigate the mechanism of action and therapeutic potential of novel splicing modulators.

    Main Methods:

    • Chemical modification of risdiplam to create CP3, a selective PRNP splicing modulator.
    • Assessing CP3's efficacy in reducing PrP levels in cellular and transgenic mouse models.
    • Investigating the role of alternative splicing factor Luc7L in CP3's activity.

    Main Results:

    • CP3 selectively activated a cryptic exon in PRNP, leading to mRNA degradation and a ~70% reduction in cellular PrP.
    • CP3's activity was dependent on the alternative splicing factor Luc7L.
    • Co-administration of CP3 and a Luc7L activator (PTC258) significantly reduced PrP levels in mouse brains.

    Conclusions:

    • Splicing modulation is a potent strategy for reducing PrP and offers a promising therapeutic avenue for prion diseases.
    • Small-molecule cooperativity can enhance therapeutic RNA targeting, exemplified by the combined use of CP3 and PTC258.