The role of Tudor family proteins in piRNA biogenesis and genome defense.

• Applicant: Professorin Dr. Teresa Carlomagno
• Subject Area: Structural Biology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 310347643

piRNAs form a recently discovered class of non-coding RNAs that protect the germline genome of animals from the activity of resident transposons. They prevent genome instability and ensure faithful information transfer to the next generation. Lately, piRNA were also found in somatic cells, suggesting their role in gene expression regulation and were implicated in various diseases including infertility and cancer. However, the mechanism of production and action of piRNAs is still largely ambiguous, preventing their applications in biotechnology or medicine. Recent genomic screens have identified Tudor domain containing proteins as particularly abundant players in the piRNA pathway. By interacting with PIWIs and helicases they could mediate the assembly of various macromolecular complexes and play a central coordinating role. Only few Tudor-containing proteins have been studied in detail to date, and their diversity, specificity and molecular function remains elusive. Here, we embark in characterizing a critical Tudor-containing piRNA biogenesis factors, Qin/Kumo, using an integrated biochemistry, structural biology, and cell biology approach. We aim to understand: i) how Tudors recognize several partner proteins specifically; ii) how various Tudor domains interact and communicate with other domains; iii) how they coordinate the action of piRNA factors; iv) and what is their exact role in piRNA biogenesis. Our results will provide key insights into the still mysterious process of piRNA biogenesis, and establish general principles of Tudor function. Ultimately, this will enable the rational design of antagonists to interfere with the piRNA pathway, opening new avenues towards applications of the pathway for studying disease mechanisms, improving transposon-based genetic engineering, and even for medicine.

• DFG Programme: Research Grants