Sipani, R. | bioRxiv Science

bioRxiv2026

Serine/Threonine phosphatase PP1 is a regulator of Notch signalling.

Cell diversity generation is cardinal to the development of the functional central nervous system. The Notch pathway plays an important role in neurogenesis, spanning cell fate determination, cell death, and neural stem cell (NSC) competence switching, and is therefore highly regulated within cells. While the phosphorylation-based regulation of the pathway and its associated kinases is known, few phosphatases have been identified to counterbalance these regulations. Protein Phosphatase 1 is a member of a Serine/Threonine family of phosphatases responsible for a large majority of dephosphorylation events in the cell. In this study, we identify PP1- and its regulatory subunit, PNUTS, as novel regulators of the Notch signalling pathway during Drosophila neurogenesis. We show that PP1-87B/PNUTS positively regulate Notch signalling by dephosphorylating a highly conserved Serine residue in Su(H) to restore its DNA binding activity and thereby activating Notch downstream targets during neurogenesis. This facilitates the execution of two distinct physiological events, NSC apoptosis and competence switching, in different regions of the Drosophila CNS. We find that this regulation of the Notch pathway is also extendable to another cellular context, epithelial wing disc tissue, and critically relies on the phosphatase activity of PP1. Given that we can rescue the Notch-dependent depletion phenotypes of PP1- using its human ortholog, we believe this regulation is likely to be conserved across species during development.

developmental biology↗

bioRxiv2023

Exoribonuclease RNase R protects Antarctic Pseudomonas syringae Lz4W from DNA damage and oxidative stress

RNase R is a highly processive, 3 -5 exoribonuclease involved in RNA degradation, maturation, and processing in bacteria. In Pseudomonas syringae Lz4W, RNase R interacts with RNase E to form the RNA degradosome complex and is essential for growth at low temperature. RNase R is also implicated in general stress response in many bacteria. We show here that the deletion mutant of rnr gene (encoding RNase R) of P. syringae is highly sensitive to various DNA damaging agents and oxidative stress. RNase R is a multidomain protein comprised of CSD, RNB and S1 domains. We investigated the role of each domain of RNase R and its exoribonuclease activity in nucleic acid damage and oxidative stress response. Our results revealed that the RNB domain alone without its exoribonuclease activity is sufficient to protect against DNA damage and oxidative stress. We also show that the association of RNase R with the degradosome complex is not required for this function. Our study has discovered for the first time a hitherto unknown role of RNase R in protecting P. syringae Lz4W against DNA damage and oxidative stress. ImportanceBacterial exoribonucleases play a crucial role in RNA maturation, degradation, quality control and turnover. In this study, we have uncovered a previously unknown role of 3-5 exoribonuclease RNase R of P. syringae Lz4W in DNA damage and oxidative stress response. Here, we show that neither the exoribonuclease function of RNase R, nor its association with the RNA degradosome complex is essential for this function. Interestingly, in P. syringae Lz4W, hydrolytic RNase R exhibits physiological roles similar to phosphorolytic 3-5 exoribonuclease PNPase of E. coli. Our data suggest that during the course of evolution, mesophilic E. coli and psychrotrophic P. syringae have apparently swapped these exoribonucleases to adapt to their respective environmental growth conditions.

microbiology↗