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

Protein domains of transposable elements (TEs) and viruses increase the protein diversity of host genomes by recombining with other protein domains. By screening 10 million eukaryotic proteins, we identified several domains that define multicopy gene families and frequently co-occur with TE/viral domains. Among these, a Tc1/Mariner transposase helix-turn-helix (HTH) domain was captured by F-box genes in the Caenorhabditis genus, creating a new class of F-box genes. For specific members of this class, like fbxa-215, we found that the HTH domain is required for diverse processes including germ granule localization, fertility, and thermotolerance. Furthermore, we provide evidence that Heat Shock Factor 1 (HSF-1) mediates the transcriptional integration of fbxa-215 into the heat shock response by binding to Helitron TEs directly upstream of the fbxa-215 locus. The interactome of HTH-bearing F-box factors suggests roles in post-translational regulation and proteostasis, consistent with established functions of F-box proteins. Based on AlphaFold2 multimer proteome-wide screens, we propose that the HTH domain may diversify the repertoire of protein substrates that F-box factors regulate post-translationally. We also describe an independent capture of a TE domain by F-box genes in zebrafish. In conclusion, we identify two independent TE domain captures by F-box genes in eukaryotes and provide insights into how these novel proteins are integrated within host gene regulatory networks.

Contributor (person)

Lee, Grace Yuh Chwen

Project(s)

Priority 2: Trait Diversity and Function

Funder

Funder name	Awards
Horizon 2020, European Union	101027241
Royal Botanic Gardens Kew, United Kingdom
Wellcome Trust, United Kingdom	Investigator Award (222451/Z/21/Z) - Senior Investigator Award (219475/Z/19/Z) - Core funding to the Gurdon Institute 092096/Z/10/Z - Core funding to the Gurdon Institute 203144/Z/16/Z
Max Planck Society, Germany
Cancer Research UK, United Kingdom	C6946/A24843 - C13474/A27826