Our group is interested in unraveling the molecular determinants that allow the establishment of a potent RNA interference (RNAi) response in which small RNAs are used to silence gene expression. We particularly want to understand how small RNAs are produced and how sRNAs induce heterochromatin formation in the nuclear RNA interference pathway.

piRNAs are a specific class of small RNAs that suppress transposable elements in the reproductive tissues of animals, safeguarding genome integrity and contributing to the maintenance of fertility. We have recently characterized the piRNA precursors-binding complex and also discovered a new endoribonuclease complex, PUCH, that specifically cleaves m7-capped piRNA precursors in the nematode C. elegans (1, 2). PUCH represents a unique enzyme assembled from Schlafen domains, which have been suggested to function as nucleases with roles in innate immunity in mammals.

Moreover, I want to discuss our recent efforts in characterizing a small, abundant human protein important for forming heterochromatin. This protein functions as a versatile protein-protein interaction hub by recognizing different short linear motifs and thus might act as a driver that supports liquid-liquid phase separation and, therefore, the formation of membrane-less organelles in the nucleus.

1.     Perez-Borrajero, C., Podvalnaya, N., Holleis, K., Lichtenberger, R., Karaulanov, E., Simon, B., Basquin, J., Hennig, J., Ketting, R. F., and Falk, S. (2021) Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans. Genes Dev. 35, 1304–1323

2.     Podvalnaya, N., Bronkhorst, A. W., Lichtenberger, R., Hellmann, S., Nischwitz, E., Falk, T., Karaulanov, E., Butter, F., Falk, S., and Ketting, R. F. (2023) piRNA processing by a trimeric Schlafen-domain nuclease. Nature. 622, 402–409