Related Experiment Video
Updated: Jul 8, 2025
08:53
Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
Published on: May 16, 2017
8.7K
The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular
Federica Raguseo1,2,3, Yiran Wang4,5, Jessica Li4,5
1Imperial College London, Department of Chemistry, Molecular Sciences Research Hub, 82 Wood Lane, London, W12 0BZ, UK.
Nature Communications
|December 13, 2023
Summary
The C9orf72 gene expansion in ALS/FTD forms G-quadruplex structures. These structures drive the formation of protein-free condensates, offering potential therapeutic targets for neurodegenerative diseases.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked neurodegenerative diseases.
- The most common genetic cause is the C9orf72 gene's hexanucleotide repeat expansion.
Purpose of the Study:
- Investigate nucleic acid secondary structure formation in C9orf72 repeats.
- Determine the role of these structures in condensate generation in ALS/FTD.
Main Methods:
- Biophysical techniques to study (GGGGCC)n repeat aggregation.
- G-quadruplex (G4) selective fluorescent probe staining in human motor neurons.
- Analysis of condensate disassembly under G4-unfolding conditions.
Main Results:
- Observed significant aggregation of (GGGGCC)n repeats, forming multimolecular G-quadruplexes (mG4s).
- Condensates disassembled upon exposure to G4-unfolding conditions.
- Increased G4-structures detected in C9orf72 mutant human motor neurons within putative condensates.
Conclusions:
- RNA G-rich repeats form protein-free condensates stabilized by mG4s.
- mG4s are crucial for condensate formation in C9orf72-related ALS/FTD.
- These mG4 structures represent potential therapeutic targets.
Related Concept Videos
02:18Alternative RNA Splicing
21.2K
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...
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...
21.2K
01:31Translation
14.9K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.9K
01:32RNA Splicing
56.4K
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...
56.4K
02:35Transcription Elongation Factors
10.9K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
10.9K
02:28Leaky Scanning
5.1K
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...
5.1K
03:21RNA-seq
10.0K
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
10.0K