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Transposable elements drive regulatory and functional innovation of F box genes

ABSTRACT: 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 multi-copy 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 localisation, fertility, and thermotolerance. Furthermore, we provide evidence that HSF-1 mediates the transcriptional integration of fbxa-215 into the heat-shock response by binding to Helitron TEs directly upstream of its 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 further demonstrate that F-box genes repeatedly and independently captured TE domains throughout eukaryotic evolution, and describe an additional instance in zebrafish. In conclusion, we identify recurrent TE domain captures by F-box genes in eukaryotes and provide insights into how these novel proteins are integrated within host gene regulatory networks.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: F Butter

LAB HEAD: Falk Butter

PROVIDER: PXD048290 | Pride | 2024-12-16

REPOSITORIES: Pride

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			Action	DRS
	20211128_QEP2_FBU_FB_collabAlmeida_Celegans_01.raw	Raw
	20211128_QEP2_FBU_FB_collabAlmeida_Celegans_02.raw	Raw
	20211128_QEP2_FBU_FB_collabAlmeida_Celegans_03.raw	Raw
	20211128_QEP2_FBU_FB_collabAlmeida_Celegans_04.raw	Raw
	20211128_QEP2_FBU_FB_collabAlmeida_Celegans_05.raw	Raw

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Project description:Sensitivity and throughput of transcriptomics and proteomomics technologies have advanced tremendously in recent years. With the use of deep sequencing of RNA samples (RNAseq) and mass spectrometry technology for protein identification and quantitation, it is now feasible to compare gene and protein expression on a massive scale and on any organism for which genomic data is available. Although these technologies are currently applied to many research questions in various model systems ranging from cell cultures to the entire organism level, there are few comparative studies of these technologies in the same system, let alone on the same samples. Here we present a comparison between gene and protein expression in zebrafish embryos, which is an upcoming model in disease studies. We compared Agilent custom made expression microarrays with Illumina deep sequencing for RNA analysis, showing as expected a high degree of correlation of expression of a common set of 15,927 genes. Gene expression was also found to correlate with the abundance of 1,017 quantified proteins, with several categories of genes as exceptions. These exceptions include ribosomal proteins, histones and vitellogenins, for which biological and technical explanations are discussed. By comparing state of the art transcriptomic and proteomic technologies on samples derived from the same group of organisms we have for the first time benchmarked the differences in these technologies with regard to sensitivity and bias towards detection of particular gene categories. Our datasets submitted to public repositories are a good starting point for researchers interested in disease progression in zebrafish at a stage of development highly suited for high throughput screening technologies. The transcriptomics data is deposited in NCBI GEO. Proteomics informatics: Spectra were identified by Mascot and validated by PeptideProphet and ProteinProphet in the Trans-Proteomic Pipeline (TPP). The main search parameters are: full tryptic specificity, precursor mass searched within -0.5 to +2.5 Da, product ions within [-0.5,0.5] Da and allowing for one missed cleavage. Carbamidomethylation was assumed as the only and fixed PTM.

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Transposable elements drive regulatory and functional innovation of F box genes

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