Molecular basis of polyadenylated RNA fate determination in the nucleus
Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs[1][1],[2][2], that are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, in...
How are RNAs sorted for export vs. degradation in the nucleus? In collaboration with @heick.bsky.socialβs lab we (@clemensplaschka.bsky.social and @juliusbrennecke.bsky.social labs) discovered a direct mechanistic link between the export and decay machineries: www.biorxiv.org/content/10.1... (1/x)
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My first first-author paper is out!π
Here we propose a model where a silencing complex, PIWI*, assembles on target RNAs to recruit effectors and shut down transposon activity.
Huge thanks to the Brennecke and Plaschka labs, especially Julius and Clemens, and all co-authors!
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12/ This work is part of my PhD project at the @viennabiocenter.bsky.socialβ¬. A big Thank You to @juliusbrennecke.bsky.social and Kirsten Senti for their supervision! To my co-authors Liudmila and @86dominik.bsky.socialβ¬, and to the rest of the Brennecke lab!
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11/ All in all, our work strongly suggests that the decision to process a transcript into piRNAs is not a feature of the genomic source locus but rather a decision that is taken in the cytoplasm after export of a TE antisense-containing transcript.
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Evolution of KoRV-A transcriptional silencing in wild koalas
Koala retrovirus-A (KoRV-A) is spreading through wild koalas in a north-to-south wave while transducing the germ line, modifying the inherited genome β¦
9/ Importantly, this is not restricted to flies, Bill Theurkauf and colleagues, showed that silencing of the invading KoRV-A retrovirus in wild koala populations strongly correlates with the presence of a single antisense insertion in a host gene 3β² UTR. www.sciencedirect.com/science/arti...
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8/ Altogether, our data show that antisense insertions of TEs in host gene exons are sufficient to elicit a piRNA response, which expands the repertoire of piRNA source loci to host genes expressed in gonads in addition to βclassicalβ piRNA clusters.
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A GFP transgene containing an antisense tirant insertion in the 3'UTR can silence tirant expression. An insertion in the sense orientation does not affect the expression of tirant.
7/ To test this idea, we generated a synthetic construct in which we placed antisense tirant sequence into the 3β² UTR of a UAS-GFP transgene. When expressed in follicle cells, this transgene silenced tirant expression, confirming our model.
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6/ This led us to propose a model in which antisense piRNAs can only be generated if a TE inserts itself into a host transcription unit (gene or piRNA cluster). This generates a cytoplasmic antisense RNA that is processed into piRNAs.
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An insertion of tirant in the antisense orientation in the 3'UTR of the gene Fs(2)Ket leads to the production of piRNAs.
An ectopic copy of the gene Fs(2)Ket containing the tirant insertion is sufficient for the production of piRNAs and silencing of tirant. This requires the production of a chimeric transcript containing both the Fs(2)Ket and the tirant RNA.
5/ Surprisingly, we found that a single antisense insertion of tirant in the 3β² UTR of a host gene, Fs(2)Ket, is sufficient to trigger piRNA production and silence tirant. piRNA production from this insertion requires host gene transcription and a chimeric mRNA-TE transcript.
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4/ Some strains lack tirant insertions in flamenco or in any other known piRNAs cluster. However, they are still able to produce piRNAs and silence tirant. So where are these piRNAs coming from?
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The tirant-GFP:lacZ reporter is expressed in the somatic follicle cells of the Drosophila melanogaster ovary and is silenced by piRNAs.
3/ We first show that tirant is exclusively expressed in somatic cells of the ovary. Here, most strains also produce tirant piRNAs from tirant insertions in flamenco, the major piRNAs cluster active in that tissue. But this is not true in all strains β¦
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2/ Over the past century, several TEs invaded Drosophila melanogaster (thanks to the work of @rokofler.bsky.socialβ¬). We traced how natural strains acquired piRNA immunity against one of these TEs, tirant, an LTR retrotransposon.
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1/ How do animals develop immunity against a newly encountered transposable element from scratch? Our study reveals that the mobility of TEs is their Achilles heel, allowing hosts to develop a powerful small RNA-mediated silencing response.
www.biorxiv.org/content/10.1...
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Curating and cataloging the world's data for the fruit fly Drosophila melanogaster into our database at http://flybase.org. Aiding discovery since 1992.
Incoming Group Leader @molgen | Postdoc in the Wysocka Lab at @ Stanford. @ EMBO, @ CancerResearch, and @ Leading Edge fellow.
Gene regulation | Transposons | Human embryo development
Transposable elements, Chromatin, piRNAs, Drosophila/iGRED-Clermont FERRAND
PhD student at the Brennecke and Plaschka labs, Vienna.
Interested in RNA silencing
Assistant professor at NDSU. I love all things Drosophila & TEs & Gene regulation. Mostly bioinformatics but you'll find me with a pipette.
Epithelial morphogenesis, microscopy and image analysis. Cytoskeleton and cell adhesion. Author of pyjamas.readthedocs.io and bitbucket.org/rfg_lab/junkie. Keeping a group of brilliant scientists entertained at www.quantmorph.ca. Also marathons and sushi.
Studying genomics, machine learning, and fruit. My code is like our genomes -- most of it is junk.
Assistant Professor UMass Chan, Board of Directors NumFOCUS
Previously IMP Vienna, Stanford Genetics, UW CSE.
A bio-physicist turned phys-biologist,
building models and software in genome biology.
3D genome structure in mitosis | DNA repair | meiosis.
A group leader at @IMBA_Vienna.
Dad x2.
Studying transposon biology, piRNA pathway, epigenetic and Drosophila germline development.
Computational biologist interested in deciphering the genomic regulatory code at vib.ai
Genetic conflict | Structural biology
Developmental Biologist working at the Francis Crick Institute. Neural tube, morphogens, and gene regulatory networks. Editor-in-chief, Development.
London Β· briscoelab.org
Incoming group leader @FMI, Basel
Postdoc @MPI-MG, Berlin | PhD @IMBA, Vienna
Investigating cell fate and loss in tissue dynamics
https://www.fmi.ch/research-groups/groupleader.html?group=150
Group leader in Cambridge (UK), interested in germline biology |epigenetics | transposons | development and more
Misses Rio on a daily basis π§π·
Vienna BioCenter Scientific Training Unit, we share opportunities that exist at the Vienna BioCenter (VBC), which include our PhD, Post Doc and Summer School programs. https://training.vbc.ac.at/
Transposable Element, piRNA & Drosophila #GReD #UCA, #Clermont-Ferrand