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Retrotransposon-derived transcripts and their functions in immunity and disease
1Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University.
Genes & Genetic Systems
|January 10, 2024
Summary
Retrotransposons, mobile genetic elements in the human genome, can trigger innate immune responses by mimicking pathogens. Their aberrant expression links to diseases, but they also play key roles in immune system development and function.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- Retrotransposons comprise ~42% of the human genome and are recognized as pathogen-associated molecular patterns (PAMPs) due to their viral sequences.
- Aberrant retrotransposon expression, often due to epigenetic dysregulation in conditions like cancer and viral infections, activates innate immunity via pattern recognition receptors (PRRs).
- This viral mimicry by retrotransposons is implicated in aging and autoimmune diseases, highlighting their complex role in host defense.
Approach:
- This review synthesizes current research on retrotransposon-derived transcripts and their immunomodulatory functions.
- It examines retrotransposons as targets of immune recognition and their association with various diseases.
- The review also explores the underappreciated impact of chimeric transcripts formed between retrotransposons and host mRNAs on immune gene isoforms and overall immune function.
Key Points:
- Retrotransposons can act as PAMPs, initiating inflammatory responses through PRR activation.
- Impaired epigenetic suppression leads to aberrant retrotransposon expression, contributing to disease pathogenesis.
- Emerging evidence indicates retrotransposons possess regulated immune reactivity and are crucial for immune system development and homeostasis.
Conclusions:
- Retrotransposon-derived transcripts exert significant and diverse effects on immune system function.
- Understanding these transcripts is vital for deciphering their role in immune defense and disease.
- Further research into retrotransposon-host interactions may reveal novel therapeutic targets for immune-related disorders.
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