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Related Concept Videos

RNA Splicing01:32

RNA Splicing

55.9K
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 Splicing02:18

Alternative RNA Splicing

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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.
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...
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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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Related Experiment Video

Updated: May 28, 2025

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay
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Transcriptome-wide alternative splicing and transcript-level differential expression analysis of post-mortem Lewy

Thomas R Goddard1, Keeley J Brookes2, Kevin Morgan3

  • 1Institute of Mental Health, Mental Health and Clinical Neurosciences Academic Unit, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.

Acta Neuropsychiatrica
|February 9, 2025
PubMed
Summary
This summary is machine-generated.

Lewy body dementias (LBD) show widespread RNA splicing changes. Transcript-level analysis reveals specific differentially expressed transcripts crucial for LBD pathology and potential biomarkers.

Keywords:
GABRB3Lewy body dementiaRNA-sequencingTMEM18alternative splicing

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Lewy body dementias (LBD) are the second most common dementia, with poorly understood molecular pathology.
  • RNA splicing dysregulation is prevalent in LBD brains, suggesting a role in disease mechanisms.

Purpose of the Study:

  • To conduct the first transcriptome-wide, transcript-level differential expression analysis in post-mortem LBD brains.
  • To identify novel therapeutic targets and biomarkers for LBD by examining RNA alterations.

Main Methods:

  • Utilized next-generation RNA-sequencing data from anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) of LBD patients and controls.
  • Employed Salmon for transcript quantification, edgeR for differential expression analysis, and DRIMseq for alternative splicing analysis.

Main Results:

  • Identified 74 differentially expressed transcripts (DET) in ACC and 96 in DLPFC.
  • Discovered 135 alternatively spliced genes in ACC and 98 in DLPFC of LBD brains.
  • Found DET potentially impacting DNA repair, apoptosis, neuroplasticity, and RNA regulation.

Conclusions:

  • Transcript-level analysis reveals DET missed by gene-level studies, offering deeper insights into LBD molecular pathology.
  • Widespread alternative splicing is confirmed, with no evidence of chronic neuroinflammation.
  • Specific DET, particularly from TMEM18, MICB, MPO, and GABRB3, show promise as LBD biomarkers and therapeutic targets.