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Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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Ribosome Profiling02:24

Ribosome Profiling

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
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RNA Splicing01:32

RNA Splicing

60.2K
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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pre-mRNA Processing02:01

pre-mRNA Processing

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
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Related Experiment Video

Updated: Jan 8, 2026

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
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Decoding ALS from the tail end of RNA.

Yusuke Fujioka1, Shinsuke Ishigaki1

  • 1Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

Cell Genomics
|December 11, 2025
PubMed
Summary

Researchers created a single-nucleus transcriptomic atlas of ALS/FTLD brain tissue. They discovered widespread changes in alternative polyadenylation, linking RNA processing to disease mechanisms.

Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are debilitating neurodegenerative diseases with complex genetic and molecular underpinnings.
  • Understanding the molecular mechanisms driving neuronal dysfunction and death in ALS/FTLD is crucial for developing effective therapies.

Purpose of the Study:

  • To generate a comprehensive single-nucleus transcriptomic atlas of the human brain affected by ALS/FTLD.
  • To investigate the role of alternative polyadenylation (APA) in the molecular pathology of ALS/FTLD.

Main Methods:

  • Single-nucleus RNA sequencing (snRNA-seq) was performed on postmortem brain tissue from individuals with ALS/FTLD and control subjects.
  • Bioinformatic analyses were used to identify differentially expressed genes and APA events across different cell types.

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Production of RNA for Transcriptomic Analysis from Mouse Spinal Cord Motor Neuron Cell Bodies by Laser Capture Microdissection
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Main Results:

  • A detailed transcriptomic atlas of ALS/FTLD brain was constructed, revealing cell-type-specific gene expression patterns.
  • Widespread alterations in alternative polyadenylation were observed in neurons and other brain cells in ALS/FTLD.
  • APA changes were found to be associated with stress responses and pathways implicated in neurodegeneration.

Conclusions:

  • Alternative polyadenylation is a significant molecular mechanism dysregulated in ALS/FTLD.
  • 3' end RNA processing acts as a key integrator of cellular stress, cell-type identity, and disease susceptibility in the brain.
  • These findings provide novel mechanistic insights into ALS/FTLD pathogenesis and suggest potential therapeutic targets related to RNA processing.