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Related Concept Videos

Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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...
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,...
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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.
Cis-acting Elements involved in mRNA stability
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

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Related Experiment Video

Updated: Jul 16, 2026

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Targeted α-synuclein mRNA degradation by PMO-based RNA-degrading chimeras.

Ning Wang1,2, Shalakha Hegde3, Zhichao Tang3

  • 1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Proceedings of the National Academy of Sciences of the United States of America
|July 14, 2026
PubMed
Summary

Researchers developed novel RNA-degrading chimeras (RDCs) to target alpha-synuclein (αSyn) mRNA, effectively reducing αSyn levels and preventing neurotoxicity in models of alpha-synucleinopathies.

Keywords:
Parkinson’s diseaseRNA-degrading chimeraRNase Lphosphorodiamidate morpholino oligomer (PMO)α-synuclein

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Investigation of RNA Synthesis Using 5-Bromouridine Labelling and Immunoprecipitation
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Investigation of RNA Synthesis Using 5-Bromouridine Labelling and Immunoprecipitation

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Last Updated: Jul 16, 2026

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

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

Investigation of RNA Synthesis Using 5-Bromouridine Labelling and Immunoprecipitation
09:59

Investigation of RNA Synthesis Using 5-Bromouridine Labelling and Immunoprecipitation

Published on: May 3, 2018

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Drug Discovery

Background:

  • Alpha-synucleinopathies are neurodegenerative diseases marked by pathological alpha-synuclein (αSyn) accumulation.
  • Directly targeting αSyn is challenging due to its disordered structure and delivery issues.
  • Targeting the SNCA transcript offers a potential therapeutic avenue.

Purpose of the Study:

  • To develop and optimize RNA-degrading chimeras (RDCs) targeting SNCA mRNA for treating alpha-synucleinopathies.
  • To assess the efficacy of RDCs in reducing αSyn expression and mitigating neurotoxicity in cellular and animal models.

Main Methods:

  • Designed and evaluated phosphorodiamidate morpholino oligonucleotide (PMO)-based RNA-degrading chimeras (RDCs).
  • Tested RDC efficacy in reducing SNCA mRNA and αSyn protein in cell lines, primary neurons, and human induced pluripotent stem cell-derived neurons.
  • Assessed RDC impact on αSyn seeding and neuronal protection in vitro, and αSyn mRNA levels in vivo.

Main Results:

  • Optimized RDC, named 4-D1, selectively degraded SNCA mRNA and reduced αSyn protein expression in an RNase L-dependent manner.
  • 4-D1 demonstrated efficacy in humanized SNCA mouse and human iPSC-derived neuronal models.
  • Reduced αSyn levels prevented prion-like seeding and protected neurons from cytotoxicity; in vivo studies confirmed efficacy.

Conclusions:

  • PMO-based RDCs, specifically 4-D1, are effective in reducing SNCA mRNA and αSyn protein levels.
  • This approach shows promise in preventing αSyn aggregation and neurotoxicity.
  • PMO-based RDCs represent a potential therapeutic strategy for alpha-synucleinopathies.