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Human TRIM5α senses and restricts LINE-1 elements.
Bianca Volkmann1, Sabine Wittmann1, Justine Lagisquet1
1Institute of Clinical and Molecular Virology, Friedrich Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
Summary
The intrinsic immune factor TRIM5α restricts and senses LINE-1 retroelements in human cells. This interaction activates innate immune signaling, protecting genomic integrity from mobile genetic elements.
Area of Science:
- Genetics
- Molecular Biology
- Immunology
Background:
- Mobile genetic elements, particularly LINE-1 retroelements, are active in the human genome.
- LINE-1 retrotransposition can cause detrimental genomic consequences.
- Cells possess mechanisms to control LINE-1 activity to maintain genome stability.
Purpose of the Study:
- To investigate the role of the intrinsic immune factor TRIM5α in controlling LINE-1 retroelements.
- To determine if TRIM5α can sense and restrict human LINE-1 retrotransposition.
- To elucidate the mechanisms by which TRIM5α interacts with and regulates LINE-1.
Main Methods:
- Cell-based assays to assess LINE-1 retrotransposition.
- Co-immunoprecipitation to study TRIM5α-LINE-1 interactions.
- Analysis of innate immune signaling pathways (AP-1, NF-κB) activation.
Main Results:
- Both human and rhesus TRIM5α efficiently repress human LINE-1 retrotransposition.
- TRIM5α interacts with LINE-1 ribonucleoprotein complexes in the cytoplasm, which is crucial for restriction.
- TRIM5α engagement with LINE-1 triggers innate immune signaling, activating AP-1 and NF-κB, leading to LINE-1 promoter down-regulation.
Conclusions:
- TRIM5α acts as a pattern recognition receptor that restricts and senses LINE-1 retroelements.
- TRIM5α employs distinct mechanisms to control LINE-1, safeguarding the human genome.
- This study reveals a novel role for TRIM5α in defending against mobile genetic elements.
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