Abstract

Most genomes contain high numbers of transposable elements: segments of DNA that can multiply themselves within and between genomes. The activity of these elements needs to be controlled, especially in germ cells, as without such control massive DNA damage, apoptosis and eventually sterility are the result. An important line of defense against transposons rests on a mechanism that is guided by small RNA molecules, named piRNAs, that bind to specific proteins, named Piwi proteins, that effective silence their targets. We recently identified the protein complex PETISCO that is required to make piRNAs in the nematode C. elegans. Interestingly, besides being involved in piRNA processing, it also acts in another, yet undefined RNA processing pathway, which we know is essential for embryogenesis. This project aims to functionally characterize of PETISCO, both in vitro as well as in vivo, with the aim to understand how it works and what RNA processing pathway it regulates during embryogenesis. We hope to delineate why these two different functions converge on one and the same complex, and through that to better understand how certain transcripts are selected to be turned into piRNAs and others not. Since the piRNA pathway fully relies on piRNA identity for its target specificity, this process is of utmost importance, and insights into this process will help to resolve how cells can recognize endogenous parasites, such as transposons.

Project-related publications

Almeida MV, Dietz S, Redl S, Karaulanov E, Hildebrandt A, Renz C, Ulrich HD, König J, Butter F, Ketting RF.
GTSF-1 is required for formation of a functional RNA-dependent RNA Polymerase complex in Caenorhabditis elegans. EMBO J. 2018 Jun 15;37(12):e99325. doi: 10.15252/embj.201899325.

Cordeiro Rodrigues RJ, de Jesus Domingues AM, Hellmann S, Dietz S, de Albuquerque BFM, Renz C, Ulrich HD, Sarkies P, Butter F, Ketting RF.
PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability. Genes Dev. 2019 Jul 1;33(13-14):857-870. doi: 10.1101/gad.322446.118.

de Albuquerque BF, Luteijn MJ, Cordeiro Rodrigues RJ, van Bergeijk P, Waaijers S, Kaaij LJ, Klein H, Boxem M, Ketting RF.
PID-1 is a novel factor that operates during 21U-RNA biogenesis in Caenorhabditis elegans. Genes Dev. 2014 Apr 1;28(7):683-8. doi: 10.1101/gad.238220.114.

de Albuquerque BF, Placentino M, Ketting RF.
Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans. Dev Cell. 2015 Aug 24;34(4):448-56. doi: 10.1016/j.devcel.2015.07.010.