Biology subjects

Lichtenberger, R.

Publications and source records attributed to Lichtenberger, R..

3 recordsLinked to original sources

bioRxiv2023

MUT-7 exoribonuclease activity and localisation are mediated by an ancient domain

The MUT-7 family of 3-5 exoribonucleases is evolutionarily conserved across the animal kingdom and plays essential roles in small RNA production in the germline. Most MUT-7 homologs carry a C-terminal domain of unknown function named MUT7-C appended to the exoribonuclease domain. Our analysis shows that the MUT7-C is evolutionary ancient, as a minimal version of the domain exists as an individual protein in prokaryotes. In animals, MUT7-C has acquired an insertion that diverged during evolution, expanding its functions. C. elegans MUT-7 contains a specific insertion within MUT7-C, which allows binding to MUT-8 and, consequently, MUT-7 recruitment to germ granules. In addition, in C. elegans and human MUT-7, the MUT7-C domain contributes to RNA binding and is thereby crucial for nuclease activity. This RNA-binding function most likely represents the ancestral function of the MUT7-C domain. Overall, this study sheds light on MUT7-C and assigns two functions to this previously uncharacterised domain.

biochemistry↗

bioRxiv2023

piRNA processing by a trimeric Schlafen-domain nuclease

Transposable elements are genomic parasites that expand within and spread between genomes1. Piwi proteins control transposon activity, notably in the germline2,3. These proteins recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. While the processing of piRNA precursors is an essential step in this process, many molecular details of this process remain unknown. We identify a novel endoribonuclease, PUCH, that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain proteins (SLFL proteins), executes 5-end piRNA precursor cleavage. PUCH-mediated processing strictly requires an m7G-Cap and a uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds piRNA precursors4, and that this interaction enhances piRNA production in vivo. The identification of PUCH completes the repertoire of C. elegans piRNA biogenesis factors and uncovers a novel type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (Slfn) genes have been associated with immunity responses5, exposing a thus far unknown molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.

molecular biology↗

bioRxiv2021

The CHK-2 antagonizing phosphatase PPM-1.D regulates meiotic entry via catalytic and non-catalytic activities

The transition from the stem cell/progenitor fate to meiosis is mediated by several redundant post-transcriptional regulatory pathways in C. elegans. Interfering with all three branches causes tumorous germlines. SCFPROM-1 comprises one branch and mediates a scheduled degradation step at entry into meiosis. prom-1 mutants show defects in timely initiation of events of meiotic prophase I, resulting in high rates of embryonic lethality. Here, we identify the phosphatase PPM-1.D/Wip1 as crucial substrate for PROM-1. We report that PPM-1.D antagonizes CHK-2 kinase, a key regulator for meiotic prophase initiation e.g., DNA double strand breaks, chromosome pairing and synaptonemal complex formation. We propose that PPM-1.D controls the amount of active CHK-2 by both catalytic and non-catalytic activities, where strikingly the non-catalytic regulation seems to be crucial at meiotic entry. PPM-1.D sequesters CHK-2 at the nuclear periphery and programmed SCFPROM-1 mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.

cell biology↗