Biology subjects

Rafanel, B.

Publications and source records attributed to Rafanel, B..

4 recordsLinked to original sources

bioRxiv2026

Identification of cis-regulatory modules responding to positional cues regulating the patterned expression of the Drosophila follicle cell fate determinants mid and mirr.

In the Drosophila ovary, the developing oocyte secretes a localized inductive signal, Gurken (Grk), that activates the Drosophila epidermal growth factor receptor (EGFR) within the overlying follicular epithelium. Grk localization is dynamic, and Grk/EGFR signaling leads to different outcomes depending on the timing and location of signaling. In early stages, Grk is localized at the posterior and induces a posterior fate characterized by expression of the T-box transcription factors midline (mid) and H15. Later, Grk adopts a dorsal anterior localization and induces the dorsal anterior fate determinant mirror (mirr), a homeodomain transcription factor. These context-dependent outcomes of Grk/EGFR signaling are mutually exclusive, raising the question of how the choice of target gene expression is regulated. We showed previously that these alternative signalling outcomes are determined by localized antiparallel gradients of posterior JAK/STAT and anterior BMP pathway activity, and mutual repression between Mid/H15 and Mirr. These regulatory interactions define a genetic network that acts as a bistable switch that toggles between alternative EGFR signaling outcomes. We hypothesize that this spatial information is ultimately interpreted by regulatory elements associated with the mid, H15 and mirr loci, but at what level these multiple cues are integrated to generate these outcomes is unclear. To approach this question, here we screen two genome-wide collections of transcriptional reporters for those bearing genomic regions from the H15, mid and mirr loci and expressed in a pattern resembling that of the endogenous gene. Here we characterize the expression of four such putative cis-regulatory regions, two from the mid locus and two from the mirr locus and test their response to the known upstream regulators in this patterning network. We find that each reproduces distinct aspects of the expression and response of the endogenous gene, with some emerging features that suggest that these regions do not function strictly modularly. These data identify genomic sequences that drive patterned expression in this tissue and provide a simplified system for asking whether these sequences are directly regulated by the upstream spatial cues in this patterning network.

developmental biology↗

bioRxiv2025

Antisense transposon insertions into host genes trigger piRNA mediated immunity

Transposable elements pose a persistent threat to genome integrity, yet how host defense systems adapt to newly invading elements remains poorly understood. Here, we reveal how Drosophila melanogaster acquired PIWI-interacting RNA (piRNA)-mediated immunity against the recently invading endogenous retrovirus tirant. By integrating genetics, small RNA profiling, and population genomics, we identify two distinct modes of de novo piRNA biogenesis. The primary mechanism involves antisense insertions into the flamenco cluster, a well-established master locus for transposon control. Strikingly, we also find that antisense tirant insertions into 3' UTRs of host genes robustly trigger piRNA production, a process driven by host gene transcription but independent of gene identity. These findings challenge prevailing models that link piRNA precursor specification to genomic origin or nuclear processing context. Instead, they uncover a flexible, general mechanism in which transposition into host gene exons represents a critical vulnerability for transposons: by generating chimeric antisense transcripts that are exported to the cytoplasm, transposons inadvertently initiate their own silencing, enabling rapid and adaptive genome defense against new invaders.

genetics↗

bioRxiv2025

Direct cell-to-cell transmission of retrotransposons

Transposable elements are abundant in host genomes but are generally considered to be confined to the cell in which they are expressed, with the notable exception of endogenous retroviruses. Here, we identify a group of LTR retrotransposons that infect the germline from somatic cells within the Drosophila ovary, despite lacking the fusogenic Envelope protein typically required for retroviral entry. Instead, these elements encode a short transmembrane protein, sORF2, with structural features reminiscent of viral cell-cell fusogens. Through genetics, imaging, and electron microscopy, we show that sORF2 localizes to invasive somatic protrusions, enabling the direct transfer of retrotransposon capsids into the oocyte. Remarkably, sORF2-like proteins are widespread among insect retrotransposons and also occur in piscine nackednaviruses and avian picornaviruses. These findings reveal a noncanonical, Envelope-independent transmission mechanism shared by retrotransposons and non-enveloped viruses, offering important insights into host-pathogen evolution and soma-germline interactions.

genetics↗

bioRxiv2023

Functional Adaptations of Endogenous Retroviruses to the Drosophila Host Underlie their Evolutionary Diversification

Transposable elements profoundly affect the biology and evolution of their hosts, yet their own evolutionary dynamics remain poorly understood. Here, we investigate insect endogenous retroviruses (iERVs), a monophyletic group of LTR retrotransposons that have acquired the trait of infectivity, likely through capture of a Baculovirus envelope gene. In Drosophila ovaries, iERVs with functional envelope have adapted their cis-regulatory sequences to be expressed in any somatic cell type, from where they infect the germline. Strikingly, related retroviruses show distinct expression patterns, indicating niche partitioning. In contrast, all non-infectious iERVs that emerged through secondary envelope-loss are specifically expressed in the germline. Co-evolving with iERVs, the genome-protecting piRNA pathway has assimilated iERV promoter and sequence information into piRNA clusters, underscoring the functional significance of iERV expression in somatic niches. We propose that the evolutionary innovation of cell-to-cell infectivity has triggered the adaptive radiation of iERVs through trait diversification and antagonistic virus-host interactions, processes that likely underpin niche-specific expression of endogenous retroviruses in vertebrates as well.

evolutionary biology↗