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Related Concept Videos

Overview of Transposition and Recombination02:13

Overview of Transposition and Recombination

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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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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.
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What is Gene Expression?01:36

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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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Updated: Oct 18, 2025

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
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Transcriptome analyses reveal tau isoform-driven changes in transposable element and gene expression.

Jennifer Grundman1, Brian Spencer1, Floyd Sarsoza1,2

  • 1Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States of America.

Plos One
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Summary

Different tau protein isoforms contribute to neurodegenerative tauopathies by altering gene expression and activating transposable elements. This study reveals isoform-specific effects on cell damage and transposable element dysregulation, mirroring patterns in Alzheimer's disease.

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Alternative splicing of the MAPT gene generates tau protein isoforms implicated in tauopathies, a class of untreatable neurodegenerative diseases.
  • Non-canonical functions of tau, including the activation of transposable elements, are gaining attention for their potential role in disease pathology.

Purpose of the Study:

  • To investigate the specific roles of different tau isoforms in promoting cell damage and regulating gene expression and transposable elements.
  • To examine tau isoform-specific and locus-specific effects on transposable element dysregulation and cellular pathology.

Main Methods:

  • Immunofluorescence, Western blot, and cytotoxicity assays were performed on differentiated SH-SY5Y cells.
  • Paired-end RNA sequencing was conducted on cells infected with tau isoform lentiviral constructs and treated with amyloid-beta oligomers.
  • Transcriptomic findings were validated using public RNA-sequencing data from Alzheimer's disease, progressive supranuclear palsy, and control human samples.

Main Results:

  • Overexpression of distinct tau isoforms and their interaction with amyloid-beta induced isoform-specific transcriptomic changes in SH-SY5Y cells.
  • Locus-specific transposable element dysregulation patterns, particularly involving L1 and Alu sites, were observed, paralleling those in Alzheimer's disease and progressive supranuclear palsy.
  • Differential rates of cell death were observed based on tau isoform overexpression, indicating isoform-specific cellular toxicity.

Conclusions:

  • Examining the roles of individual tau isoforms is crucial for understanding neurodegeneration in tauopathies.
  • Transposable element dysregulation driven by tau isoforms may contribute to neuroinflammation and pathology in tauopathies.
  • These findings highlight the significance of transposable element dysregulation in the innate immune response within neurodegenerative contexts.