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Related Concept Videos

RNA Splicing01:32

RNA Splicing

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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...
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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.
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Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
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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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Related Experiment Video

Updated: Nov 9, 2025

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
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AIF3 splicing switch triggers neurodegeneration.

Shuiqiao Liu1,2, Mi Zhou1,2, Zhi Ruan1,2

  • 1Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Molecular Neurodegeneration
|April 15, 2021
PubMed
Summary

Researchers identified a novel AIF3 splicing isoform that triggers neurodegeneration in the brain. This discovery, linked to mitochondrial dysfunction and nuclear translocation, offers potential therapeutic targets for diseases like stroke.

Keywords:
AIFAIF3 splicingMitochondrial dysfunctionNeurodegeneration

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Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay
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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Apoptosis-inducing factor (AIF) is crucial for cell survival and death.
  • AIF's role in neurodegeneration under pathological conditions is not fully understood.
  • Alternative splicing of AIF may influence its function in the brain.

Purpose of the Study:

  • To identify AIF splicing isoforms induced under pathological conditions.
  • To investigate the impact of AIF splicing on mitochondrial function and neurodegeneration.
  • To establish a mouse model for studying AIF splicing-induced neurodegeneration.

Main Methods:

  • Utilized 5' RACE, Sanger sequencing, and proteomics to identify AIF isoforms.
  • Employed splicing-specific PCR and cell death assays.
  • Developed and analyzed three distinct mouse models: harlequin, AIF3 knockin, and conditional inducible AIF splicing models.

Main Results:

  • Identified a novel AIF isoform, AIF3 (lacking exons 2 and 3), upregulated post-stroke in human and mouse brains.
  • AIF3 splicing in mice led to severe neurodegeneration, enlarged ventricles, and premature death.
  • AIF3 inhibited mitochondrial functions (NADH oxidase, ATP production, oxygen consumption) and promoted nuclear translocation, causing neuronal cell death.

Conclusions:

  • AIF3 is a disease-inducible isoform contributing to neurodegeneration.
  • AIF3 splicing-induced neurodegeneration results from synergistic mitochondrial dysfunction and nuclear translocation.
  • The AIF3 splicing mouse model provides a tool for studying neurodegenerative diseases and identifying therapeutic targets.