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The reverse transcriptase-RNase H: from viruses to antiviral defense
Karin Moelling1, Felix Broecker
1Max Planck Institute for Molecular Genetics, Berlin, Germany; Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; Heinrich Pette Institute, Hamburg, Germany.
Annals of the New York Academy of Sciences
|February 24, 2015
Summary
Reverse transcriptase and RNase H-like enzymes were crucial for the RNA to DNA world transition. These enzymes, alongside small interfering RNA (siRNA) systems, shape genomes and provide antiviral defense.
Area of Science:
- Molecular Biology
- Genomics
- Virology
Background:
- Reverse transcriptase and RNase H-like activities are ancient enzymes involved in genome evolution.
- These enzymes are integral to cellular defense mechanisms against viruses and mobile genetic elements.
- Endogenous retroviruses (ERVs) and transposable elements (TEs) are shaped by these enzymatic activities.
Purpose of the Study:
- To explore the evolutionary roles of reverse transcriptase and RNase H-like enzymes.
- To investigate the connection between retroviral components and antiviral defense systems, particularly small interfering RNA (siRNA).
- To highlight the homology between siRNA, interferon response, and CRISPR systems.
Main Methods:
- Comparative genomics analysis to identify homologies between viral and cellular defense machinery.
- Literature review and analysis of existing data on enzyme functions and evolutionary pathways.
- Functional assays (e.g., Dicer knockdown) to demonstrate the activity of siRNA machinery in mammalian cells.
Main Results:
- Reverse transcriptase and RNase H-like enzymes played a key role in the RNA-to-DNA world transition.
- A significant overlap exists between retroviral components and the siRNA antiviral machinery.
- RNase H-like enzymes are central to various antiviral systems, including CRISPR and immunoglobulin rearrangement.
- siRNA machinery remains active in mammalian cells, impacting viral replication and apoptosis.
- Homologies were observed between siRNA, interferon response, siDNA, and CRISPR systems.
- ERVs exhibit roles in defense, gene regulation, and cancer.
Conclusions:
- Ancient enzymes like reverse transcriptase and RNase H are fundamental to genome structure and defense.
- The siRNA pathway shares deep evolutionary roots with other defense systems, including CRISPR.
- Understanding these conserved mechanisms offers insights into genome evolution and disease.
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