Related Experiment Video
Updated: Jun 5, 2025
07:14
Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
Published on: February 25, 2022
5.9K
RNA Isoform Diversity in Human Neurodegenerative Diseases
Christine S Liu1,2, Chris Park1,2, Tony Ngo1
1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037.
Eneuro
|December 10, 2024
Summary
This study combines short-read and long-read sequencing to analyze mRNA isoforms in the human brain, revealing extensive isoform diversity in neurological diseases like Alzheimer's, dementia with Lewy bodies, and Parkinson's disease.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Single-nucleus RNA-sequencing (snRNA-seq) using short reads offers cellular insights but misses full-length mRNA isoforms.
- Understanding mRNA isoform diversity is crucial for comprehending brain complexity and neurological diseases.
Purpose of the Study:
- To investigate full-length mRNA isoform diversity in single human brain cells across neurodegenerative diseases.
- To link cell types with specific isoform expression patterns for disease-related genes.
Main Methods:
- Combined standard 10x Genomics short-read snRNA-seq with targeted PacBio long-read snRNA-seq.
- Analyzed prefrontal cortex samples from 25 donors with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and controls.
- Utilized enrichment probes for 50 disease-related genes followed by long-read sequencing.
Main Results:
- Identified shared and distinct gene expression changes across AD, DLB, and PD using short-read data.
- Revealed vast mRNA isoform diversity for all 50 targeted genes, even those not differentially expressed in short-read data.
- Developed a novel informatics method for detecting isoform structural differences.
Conclusions:
- The study provides an expanded single-cell transcriptomic dataset for the human prefrontal cortex across major neurodegenerative diseases.
- Increased mRNA isoform diversity may contribute to disease pathology and represents potential therapeutic targets.
Keywords:
Alzheimer’s diseaseParkinson’s diseaseRNA-seqdementia with Lewy bodiesisoformslong-read sequencingMore Related Videos
Related Concept Videos
01:32RNA Splicing
56.0K
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...
56.0K
02:18Alternative RNA Splicing
21.0K
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...
21.0K
01:37Neural Regulation
39.1K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.1K
01:31Translation
14.5K
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...
14.5K
03:03Amyloid Fibrils
9.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
02:32Exon Recombination
3.5K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.5K