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Siqueira de Oliveira, D.

Publications and source records attributed to Siqueira de Oliveira, D..

3 recordsLinked to original sources

A trans-piRNA network and transcriptional antagonism shape piRNA cluster function

PIWI-interacting (pi)RNAs protect animal germlines from transposable elements (TEs) by guiding their sequence-specific repression. In Drosophila germline, piRNAs are encoded in distinct genomic regions, piRNA clusters (piCs), that are transcribed by a non-canonical machinery that is anchored on chromatin by the HP1 paralogue Rhino. Studies of transgenic piCs revealed that piRNA biogenesis depends on cytoplasmic inheritance of piRNAs, however, whether native piCs require trans-generational piRNA transmission remained unknown. Here, we used two approaches to show that cytoplasmic inheritance of cognate piRNAs is critical for piRNA biogenesis. Our analyses reveal that individual piCs form a tightly interconnected network linked by trans-acting piRNAs that reinforce biogenesis. According to the transposon trap model, the content of piCs is updated by integration of novel TEs leading to production of piRNA guides against integrated transposons. However, we found that transcription driven by promoters integrated into piCs disrupt local piRNA biogenesis by removing Rhino and antagonizing non-canonical transcription of piRNA precursors. Thus, newly inserted transposons might suppress piRNA production before they become domesticated by the piRNA pathway calling for a revision of the trap model. Together, our results reveal that piC activity is shaped by transcriptional competition and a dynamic interplay between individual piCs connected into a common network. HighlightsO_LICytoplasmic inheritance of maternal piRNAs is required for piRNA biogenesis in the next generation C_LIO_LITrans-acting piRNA ensure robustness of piRNA biogenesis and repression by connecting individual clusters into a functional network C_LIO_LIPing-pong amplification provides non-uniform processing of different regions inside piCs C_LIO_LIGenes can remain active inside piRNA clusters antagonizing Rhino-dependent non-canonical transcription and piRNA biogenesis, challenging the transposon trap model C_LI

molecular biology↗

A comprehensive evolutionary scenario for the origin and neofunctionalization of the Drosophila speciation gene Odysseus (OdsH)

Odysseus (OdsH) was the first gene described in Drosophila related to speciation and hybrid sterility. This gene was first described in the melanogaster subgroup and more specifically in the sterile hybrids from crosses between D. mauritiana and D. simulans. Its origin is attributed to the duplication of the gene unc-4, which would have occurred in the ancestor of the subgenus Sophophora. By using a much larger sample of Drosophila species, we showed that contrary to what has been previously proposed, OdsH origin occurred approximately 62 million years ago (Mya). Then, OdsH have experienced rapid neofunctionalization in male reproductive tracts, evidenced by its evolutionary rates, expression and transcription factor binding sites. Furthermore, the analysis of the OdsH peptide sequence allowed the identification of mutations in the DNA- and protein-binding domains of D. mauritiana that could result in incompatibility with genomes from other species. We then explored the expression of OdsH in the spermatocytes of D. arizonae and D. mojavensis, a pair of recently diverged sister species with incomplete reproductive isolation and expected to find the involvement of OdsH in hybrid sterility. Our data indicated that OdsH expression is not atypical in male-sterile hybrids from these species. In conclusion, we have demonstrated that the origin of OdsH occurred earlier than previously proposed and that its neofunctionalization in male sexual functions occurred rapidly after its origin. Our results also suggested that its role as a speciation gene, as in the melanogaster subgroup of species, may be restricted to this specific taxon.

evolutionary biology↗

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/225581v3_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@15ca5a6org.highwire.dtl.DTLVardef@17f455forg.highwire.dtl.DTLVardef@a39f50org.highwire.dtl.DTLVardef@306ec1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗