Transposable Elements Drive Regulatory and Functional Innovation of F-box Genes.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Transposable elements (TEs) and viruses can increase protein diversity within host genomes through domain recombination.
• F-box genes are crucial components of ubiquitin ligase complexes involved in protein degradation.

Purpose of the Study:

• To identify instances of transposable element (TE) or viral domain capture by eukaryotic genes.
• To investigate the functional integration and regulatory roles of novel proteins arising from such captures.

Main Methods:

• Large-scale screening of 10 million eukaryotic proteins to identify co-occurring TE/viral and host domains.
• Functional characterization of specific F-box genes (e.g., fbxa-215) containing a Tc1/Mariner transposase helix-turn-helix (HTH) domain.
• Analysis of transcriptional regulation using Heat Shock Factor 1 (HSF-1) binding assays.
• Proteome-wide interaction studies using AlphaFold2 multimer predictions.

Main Results:

• Identified a Tc1/Mariner transposase helix-turn-helix (HTH) domain captured by F-box genes in Caenorhabditis, forming a new F-box gene class.
• Demonstrated that the HTH domain in fbxa-215 is essential for germ granule localization, fertility, and thermotolerance.
• Showed HSF-1 integrates fbxa-215 into the heat shock response via direct binding to upstream Helitron TEs.
• Revealed an independent capture of a TE domain by F-box genes in zebrafish.
• Interactome analysis suggests HTH-bearing F-box proteins are involved in post-translational regulation and proteostasis.

Conclusions:

• Two independent cases of TE domain capture by F-box genes in eukaryotes were identified.
• These captured domains diversify the substrate specificity of F-box proteins, impacting proteostasis.
• Novel F-box proteins are integrated into host gene regulatory networks, influencing various biological processes.